Articles de revues : « MiR-885-5p »

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Zu, Yuanqi, Qianqian Wang et Hong Wang. « Identification of miR-885-5p as a Tumor Biomarker : Regulation of Cellular Function in Cervical Cancer ». Gynecologic and Obstetric Investigation 86, n^o 6 (2021) : 525–32. http://dx.doi.org/10.1159/000520980.

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Objectives: MicroRNAs were revealed as biomarkers for early detection or prognosis predictors of cancer and were involved in the progression of cancer. The present study investigated the expression pattern and potential clinical and functional role of miR-885-5p in cervical cancer. Design: A total of 115 pairs of cervical cancer tissue specimens and adjacent nontumor paracancerous tissue specimens were collected from the cervical cancer patients who underwent surgical resection or biopsy without preoperative systemic therapy at Maternity and Child Health Care of Zaozhuang from 2012 to 2014. Participants/Materials, Setting, Methods: The expression levels of miR-885-5p in cervical cancer were measured using the qRT-PCR assay. A follow-up study was conducted, and the Kaplan-Meier method with log-rank test was used to analyze the potential clinical significance of miR-885-5p in cervical cancer. The functional experiments including CCK-8, Transwell migration, and invasion assays were used to investigate the biological function of miR-885-5p in cervical cancer cells. Results: miR-885-5p expression was decreased in tumor tissues and tumor cell lines compared to normal control. Low expression of miR-885-5p was related to lymph node metastasis, late FIGO stage, and shorter overall survival outcome. Ascending expression of miR-885-5p inhibited the proliferative, migratory, and invasive abilities of cervical cancer cells, while downregulation of miR-885-5p promoted these cellular abilities of cervical cancer cells in vitro. Limitations: The patient population size was limited; thus, the clinical significance of miR-885-5p requires further verification. Second, the precise mechanism of miR-885-5p in cervical cancer is still exclusive. In the future studies, a larger sample size will be required to confirm the prognostic value of miR-885-5p in cervical cancer, and the possible targets, as well as the detailed mechanism of miR-885-5p, will be investigated. Conclusions: miR-885-5p expression was decreased in cervical cancer, and downregulation of miR-885-5p promoted the progression of cervical cancer cells. MiR-885-5p may be an independent prognostic predictor and therapeutic target for treating cervical cancer.

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Domingo, S., C. Solé-Marcé, T. Moline, B. Ferrer et J. Cortés-Hernández. « POS0135 DOWNREGULATION OF miR-885-5p AS A KEY EFFECTOR IN CUTANEOUS LUPUS ERYTHEMATOSUS PATHOGENESIS ». Annals of the Rheumatic Diseases 81, Suppl 1 (23 mai 2022) : 294.1–295. http://dx.doi.org/10.1136/annrheumdis-2022-eular.4501.

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BackgroundSkin involvement is common in systemic lupus erythematosus (SLE), with up to 70% of patients developing skin lesions at some point during the course of their disease. Moreover, cutaneous lesions are the first sign of systemic disease in 20% of SLE patients [1]. Skin requires a regulated and undisrupted miRNA profile for a correct development and function. Studies show that miRNAs play a pathogenic role in autoimmune skin diseases such as Psoriasis [2]. Understanding of the role of deregulated miRNAs in CLE may enhance our knowledge about CLE pathogenesis which is currently not understood.ObjectivesIdentify differentially expressed miRNAs in skin lesions to determine their role in CLE pathogenesis.MethodsPaired skin biopsies from CLE lesional (n=20) and non-lesional skin (n=20) were obtained. MiRNA microarray screening was performed using TaqMan MicroRNA Array. Validation was performed in a new cohort of FFPE skin samples by qRT-PCR (n=20). In situ hybridization was performed to identify the skin cell type involved in selected miRNAs. Next, in vitro experiments using primary skin and immune cells were performed in order to discover their role in CLE pathogenesis. A microarray screening and luciferase assay were performed to find miR-885-5p altered gene expression, molecular pathways and target genes.ResultsMiR-885-5p was found downregulated in CLE lesional skin (-4.45 fold, pvalue<0,01, respectively). Results were confirmed in a validation cohort. In situ hybridization revealed miR-885-5p was located in the epidermal keratinocytes in CLE non-lesional skin. Healthy keratinocytes presented an increased miR-885-5p expression compared with other relevant cell types such as fibroblasts (p<0.001) or PBMCs (p<0.001). Moreover stimulation with IFNα and UVB promoted a marked long-lasting downregulation of miR-885-5p (IFNα, 24h -67 fold (p<0.001); UVB, 24h -70 fold (p<0.001)).Gene microarray of anti-miR-885-5p keratinocytes showed that the unique gene that was upregulated in all anti-miR-885-5p conditions was PSMB5. In vitro experiments demonstrated that PSMB5 is a direct target of miR-885-5p (74% of reduction p<0.001) and it is involved in epidermal inflammation by enhancing NFKB and inflammatory cytokines IL-1β, TNFα and CXCL8. In addition, we observed immune recruitment in UVB stimulated anti-miR885-5p keratinocytes and we found that this immune migration is mediated via miR-885-5p direct binding of TRAF1 and subsequent chemokine CCL5, CCL20, CXCL8 and S100A7 secretion.ConclusionOur findings demonstrate that CLE lesions present a downregulation of miR-885-5p that is strongly implicated in CLE pathogenesis. Moreover, miRNA applicability as therapeutics makes the discovered miRNAs promising candidates for novel therapy in CLE, as there is a need to develop new therapies for refractory cases and to avoid current treatment significant side effects.References[1]Okon LG, Werth VP. Cutaneous lupus erythematosus: diagnosis and treatment. Best Pract Res Clin Rheumatol. 2013; 27(3):391-404.[2]Sonkoly E et al. MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One. 2007. 11;2(7):e610.Disclosure of InterestsNone declared

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Gui, Junhao, Yaping Tian, Xinyu Wen, Wenhui Zhang, Pengjun Zhang, Jing Gao, Wei Run, Liyuan Tian, Xingwang Jia et Yanhong Gao. « Serum microRNA characterization identifies miR-885-5p as a potential marker for detecting liver pathologies ». Clinical Science 120, n^o 5 (19 novembre 2010) : 183–93. http://dx.doi.org/10.1042/cs20100297.

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Circulating miRNAs (microRNAs) are emerging as promising biomarkers for several pathological conditions, and the aim of this study was to investigate the feasibility of using serum miRNAs as biomarkers for liver pathologies. Real-time qPCR (quantitative PCR)-based TaqMan MicroRNA arrays were first employed to profile miRNAs in serum pools from patients with HCC (hepatocellular carcinoma) or LC (liver cirrhosis) and from healthy controls. Five miRNAs (i.e. miR-885-5p, miR-574-3p, miR-224, miR-215 and miR-146a) that were up-regulated in the HCC and LC serum pools were selected and further quantified using real-time qPCR in patients with HCC, LC, CHB (chronic hepatitis B) or GC (gastric cancer) and in normal controls. The present study revealed that more than 110 miRNA species in the serum samples and wide distribution ranges of serum miRNAs were observed. The levels of miR-885-5p were significantly higher in sera from patients with HCC, LC and CHB than in healthy controls or GC patients. miR-885-5p yielded an AUC [the area under the ROC (receiver operating characteristic) curve] of 0.904 [95% CI (confidence interval), 0.837–0.951, P<0.0001) with 90.53% sensitivity and 79.17% specificity in discriminating liver pathologies from healthy controls, using a cut off value of 1.06 (normalized). No correlations between increased miR-885-5p and liver function parameters [AFP (α-fetoprotein), ALT (alanine aminotransferase), AST (aspartate aminotransferase) and GGT (γ-glutamyl transpeptidase)] were observed in patients with liver pathologies. In summary, miR-885-5p is significantly elevated in the sera of patients with liver pathologies, and our data suggest that serum miRNAs could serve as novel complementary biomarkers for the detection and assessment of liver pathologies.

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Petric, Rok, Barbara Gazic, Katja Goricar, Vita Dolzan, Radan Dzodic et Nikola Besic. « Expression of miRNA and Occurrence of Distant Metastases in Patients with Hürthle Cell Carcinoma ». International Journal of Endocrinology 2016 (2016) : 1–6. http://dx.doi.org/10.1155/2016/8945247.

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Background. Hürthle cell thyroid carcinoma (HCTC) is a rare type of thyroid carcinoma. In the present study, we investigated whether the expression of miRNAs of interest is associated with the occurrence of metastases in patients with HCTC.Materials and Methods. In 39 patients with HCTC (22 with nonmetastatic and 17 with regional or distant metastatic disease), the expression levels of six miRNAs (miR-138, miR-183, miR-221, miR-222, miR-768-3p, and miR-885-5p) and U6 snRNA as endogenous control were determined in FFPE samples of primary tumor and normal thyroid tissue using TaqMan miRNA assays.Results. In patients with HCTC, miR-138 and miR-768-3p were downregulated in tumor samples compared to normal tissue (p=0.013andp=0.010, resp.). These two miRNAs were also significantly downregulated in tumor samples of patients with metastatic disease (p=0.030andp=0.048, resp.) but not in patients with nonmetastatic disease (p=0.249andp=0.101, resp.). In patients with nonmetastatic disease, miR-221 and miR-885-5p were slightly, albeit significantly, upregulated in tumorous compared to normal tissue (p=0.042andp=0.027, resp.).Conclusion. Expression of miRNA (miR-183, miR-221, and miR-885-5p) in tumor tissue is associated with the occurrence of distant metastases in patients with HCTC.

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Yamano, Tomoki, Shuji Kubo, Emiko Sonoda, Tomoko Kominato, Kei Kimura, Michiko Yasuhara, Kozo Kataoka et al. « Assessment of circulating microRNA specific for patients with familial adenomatous polyposis ». PLOS ONE 16, n^o 5 (4 mai 2021) : e0250072. http://dx.doi.org/10.1371/journal.pone.0250072.

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Circulating microRNAs (miRNAs) are considered promising biomarkers for diagnosis, prognosis, and treatment efficacy of diseases. However, usefulness of circulating miRNAs as biomarkers for hereditary gastrointestinal diseases have not been confirmed yet. We explored circulating miRNAs specific for patients with familial adenomatous polyposis (FAP) as a representative hereditary gastrointestinal disease. Next-generation sequencing (NGS) indicated that plasma miR-143-3p, miR-183-5p, and miR-885-5p were candidate biomarkers for five FAP patients compared to three healthy donors due to moderate copy number and significant difference. MiR-16-5p was considered as an internal control due to minimum difference in expression across FAP patients and healthy donors. Validation studies by real-time PCR showed that mean ratios of maximum expression and minimum expression were 2.2 for miR-143-3p/miR-16-5p, 3.4 for miR-143-3p/miR-103a-3p, 5.1 for miR-183-5p/miR-16-5p, and 4.9 for miR-885-5p/miR-16-5p by using the samples collected at different time points of eight FAP patients. MiR-143-3p/16-5p was further assessed using specimens from 16 FAP patients and 7 healthy donors. MiR-143-3p was upregulated in FAP patients compared to healthy donors (P = 0.04), but not significantly influenced by clinicopathological features. However, miR-143-3p expression in colonic tumors was rare for upregulation, although there was a significant difference by existence of desmoid tumors. MiR-143-3p transfection significantly inhibited colorectal cancer cell proliferation compared to control microRNA transfection. Our data suggested regulation of miR-143-3p expression differed by samples (plasma or colonic tumors) in most FAP patients. Upregulation of plasma miR-143-3p expression may be helpful for diagnosis of FAP, although suppressive effect on tumorigenesis seemed insufficient in FAP patients.

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Inomistova, M., N. Khranovska, O. Skachkova, G. Klymnyuk et S. Demydov. « Significance of miR-885-5p in neuroblastoma outcome ». Studia Biologica 9, n^o 3–4 (2015) : 23–30. http://dx.doi.org/10.30970/sbi.0903.450.

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Gioffré, Sonia, Mattia Chiesa, Daniela Maria Cardinale, Veronica Ricci, Chiara Vavassori, Carlo Maria Cipolla, Serge Masson et al. « Circulating MicroRNAs as Potential Predictors of Anthracycline-Induced Troponin Elevation in Breast Cancer Patients : Diverging Effects of Doxorubicin and Epirubicin ». Journal of Clinical Medicine 9, n^o 5 (11 mai 2020) : 1418. http://dx.doi.org/10.3390/jcm9051418.

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Anthracyclines are anti-neoplastic drugs presenting cardiotoxicity as a side effect. Cardiac troponins (cTn) and echocardiography are currently used to assess cardiac damage and dysfunction, but early biomarkers identifying patients in need of preventive treatments remain a partially met need. Circulating microRNAs (miRNAs) represent good candidates, so we investigated their possible roles as predictors of troponin elevation upon anthracycline treatment. Eighty-eight female breast cancer patients administered with doxorubicin (DOX) or epirubicin (EPI) were divided into four groups basing on drug type and cTn positive (cTn+) or negative (cTn−) levels: DOX cTn−, DOX cTn+, EPI cTn− and EPI cTn+. Blood was collected at baseline, during treatment, and at follow-up. We identified plasma miRNAs of interest by OpenArray screening and single assay validation. Our results showed miR-122-5p, miR-499a-5p and miR-885-5p dysregulation in DOX patients at T0, identifying a signature separating, with good accuracy, DOX cTn− from DOX cTn+. No miRNAs showed differential expression in EPI subjects. Conversely, an anthracycline-mediated modulation (regardless of cTn) was observed for miR-34a-5p, -122-5p and -885-5p. Our study indicates specific circulating miRNAs as possible prediction markers for cardiac troponin perturbation upon anthracycline treatment. Indeed, our findings hint at the possible future use of plasma miRNAs to predict the cardiac responsiveness of patients to different anticancer agents.

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Pirola, Carlos J., et Silvia Sookoian. « MicroRNAs as messengers of liver diseases : has the message finally been decrypted ? » Clinical Science 136, n^o 5 (mars 2022) : 323–28. http://dx.doi.org/10.1042/cs20211177.

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Abstract MicroRNAs (miRNAs), which are regarded as crucial regulators of gene expression and diverse aspects of cell biology, can be present in various body fluids as highly stable molecules. It is also known that miRNAs exert tissue-specific regulation of gene transcription. Large amount of clinical and experimental evidence provided the rationale for raising the intriguing question of whether miRNAs can mediate cell–cell communication. For those reasons, miRNAs have been considered as the ‘Holy Grail’ of biomarkers allowing non-invasive diagnostic screening and early detection of a variety of diseases, including solid and non-solid cancers. In a study published in Clin. Sci. (Lond.) (2011) 120(5):183–193 (https://doi.org/10.1042/CS20100297), Gui et al. investigated the hypothesis that circulating miRNAs could be used to identify patients with liver pathologies. Specifically, the authors profiled circulating miRNAs in patients with hepatocellular carcinoma (HCC), liver cirrhosis (LC), and healthy controls and found that serum miR-885-5p levels were significantly higher in samples of patients with HCC (6.5-fold increase) and LC (8.8-fold increase). In this commentary, we highlight biological aspects associated with mir-122-the ‘liver-specific’ miRNA, which has been associated with a diverse range of liver pathologies. In addition, we discuss the relevance of mir-885-5p as potential biomarker for detecting human cancers. Finally, we provide some clues about how presumably unrelated miRNAs such as miR-122 and miR-885-5p may act in similar biological processes (BPs), making the miRNA regulatory networks more complex than anticipated.

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Fayyad-Kazan, Mohammad, Rim ElDirani, Eva Hamade, Rania El Majzoub, Haidar Akl, Nizar Bitar, Hussein Fayyad-Kazan et Bassam Badran. « Circulating miR-29c, miR-30c, miR-193a-5p and miR-885-5p : Novel potential biomarkers for HTLV-1 infection diagnosis ». Infection, Genetics and Evolution 74 (octobre 2019) : 103938. http://dx.doi.org/10.1016/j.meegid.2019.103938.

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Hosen, Mohammed Rabiul, Philip Roger Goody, Andreas Zietzer, Xu Xiang, Sven Thomas Niepmann, Alexander Sedaghat, Vedat Tiyerili et al. « Circulating MicroRNA-122-5p Is Associated With a Lack of Improvement in Left Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles ». Circulation 146, n^o 24 (13 décembre 2022) : 1836–54. http://dx.doi.org/10.1161/circulationaha.122.060258.

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Background: Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis. A majority of patients exhibit improvements in left ventricular ejection fraction (LVEF) after TAVR in response to TAVR-associated afterload reduction. However, a specific role for circulating microRNAs (miRNAs) in the improvement of cardiac function for patients after TAVR has not yet been investigated. Here, we profiled the differential expression of miRNAs in circulating extracellular vesicles (EVs) in patients after TAVR and, in particular, the novel role of circulating miR-122-5p in cardiomyocytes. Methods: Circulating EV-associated miRNAs were investigated by use of an unbiased Taqman-based human miRNA array. Several EV miRNAs (miR-122-5p, miR-26a, miR-192, miR-483-5p, miR-720, miR-885-5p, and miR-1274) were significantly deregulated in patients with aortic valve stenosis at day 7 after TAVR compared with the preprocedural levels in patients without LVEF improvement. The higher levels of miR-122-5p were negatively correlated with LVEF improvement at both day 7 ( r =−0.264 and P =0.015) and 6 months ( r =−0.328 and P =0.0018) after TAVR. Results: Using of patient-derived samples and a murine aortic valve stenosis model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Mice with graded wire injury–induced aortic valve stenosis demonstrated a higher level of miR-122-5p, which was related to cardiomyocyte dysfunction. Murine ex vivo experiments revealed that miR-122-5p is highly enriched in endothelial cells compared with cardiomyocytes. Coculture experiments, copy-number analysis, and fluorescence microscopy with Cy3-labeled miR-122-5p demonstrated that miR-122-5p can be shuttled through large EVs from endothelial cells into cardiomyocytes. Gain- and loss-of-function experiments suggested that EV-mediated shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes. Mechanistically, mass spectrometry, miRNA pulldown, electrophoretic mobility shift assay, and RNA immunoprecipitation experiments confirmed that miR-122-5p interacts with the RNA-binding protein hnRNPU (heterogeneous nuclear ribonucleoprotein U) in a sequence-specific manner to encapsulate miR-122-5p into large EVs. On shuttling, miR-122-5p reduces the expression of the antiapoptotic gene BCL2 by binding to its 3′ untranslated region to inhibit its translation, thereby decreasing the viability of target cardiomyocytes. Conclusions: Increased levels of circulating proapoptotic EV-incorporated miR-122-5p are associated with reduced LVEF after TAVR. EV shuttling of miR-122-5p regulates the viability and apoptosis of cardiomyocytes in a BCL2-dependent manner.

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Dettmer, Matthias S., Aurel Perren, Holger Moch, Paul Komminoth, Yuri E. Nikiforov et Marina N. Nikiforova. « MicroRNA profile of poorly differentiated thyroid carcinomas : new diagnostic and prognostic insights ». Journal of Molecular Endocrinology 52, n^o 2 (17 janvier 2014) : 181–89. http://dx.doi.org/10.1530/jme-13-0266.

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The diagnosis of conventional and oncocytic poorly differentiated (oPD) thyroid carcinomas is difficult. The aim of this study is to characterise their largely unknown miRNA expression profile and to compare it with well-differentiated thyroid tumours, as well as to identify miRNAs which could potentially serve as diagnostic and prognostic markers. A total of 14 poorly differentiated (PD), 13 oPD, 72 well-differentiated thyroid carcinomas and eight normal thyroid specimens were studied for the expression of 768 miRNAs using PCR-Microarrays. MiRNA expression was different between PD and oPD thyroid carcinomas, demonstrating individual clusters on the clustering analysis. Both tumour types showed upregulation of miR-125a-5p, -15a-3p, -182, -183-3p, -222, -222-5p, and downregulation of miR-130b, -139-5p, -150, -193a-5p, -219-5p, -23b, -451, -455-3p and of miR-886-3p as compared with normal thyroid tissue. In addition, the oPD thyroid carcinomas demonstrated upregulation of miR-221 and miR-885-5p. The difference in expression was also observed between miRNA expression in PD and well-differentiated tumours. The CHAID algorithm allowed the separation of PD from well-differentiated thyroid carcinomas with 73–79% accuracy using miR-23b and miR-150 as a separator. Kaplan–Meier and multivariate analysis showed a significant association with tumour relapses (for miR-23b) and with tumour-specific death (for miR-150) in PD and oPD thyroid carcinomas. MiRNA expression is different in conventional and oPD thyroid carcinomas in comparison with well-differentiated thyroid cancers and can be used for discrimination between these tumour types. The newly identified deregulated miRNAs (miR-150, miR-23b) bear the potential to be used in a clinical setting, delivering prognostic and diagnostic informations.

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Zhang, Yang. « ATRT-01. IDENTIFICATION OF MICRORNA-BASED PROGNOSTIC BIOMARKERS AND CANDIDATE THERAPEUTIC AGENTS FOR ATYPICAL TERATOID/RHABDOID TUMOR ». Neuro-Oncology 23, Supplement_1 (1 juin 2021) : i1. http://dx.doi.org/10.1093/neuonc/noab090.001.

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Abstract Background MicroRNA (miRNA) has been found to be involved in development of many malignant pediatric brain tumors, including atypical teratoid/rhabdoid tumor (AT/RT) that is highly aggressive and carries a dismal prognosis. The current study investigated the potential value of miRNAs and pivotal genes associated with AT/RT using bioinformatics analysis, aiming to identify new prognostic biomarkers and candidate drugs for AT/RT patients. Methods Differentially expressed miRNAs (DEMs) and genes (DEGs) between AT/RT and normal control samples were obtained from GEO database. The target genes of DEMs were predicted via TargetScanHuman7.2 and miRDB, and then intersected with DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of overlapping genes were conducted, followed by construction of protein-protein interaction network. Hub genes were determined by Cytoscape software, and their prognostic values were evaluated using Kaplan-Meier analysis. Connectivity Map database was used to identify latent therapeutic agents. Results A total of 11 DEMs (hsa-miR-1224-5p, hsa-miR-128-3p, hsa-miR-17-5p, hsa-miR-18b-5p, hsa-miR-29c-5p, hsa-miR-329-3p, hsa-miR-379-5p, hsa-miR-433-3p, hsa-miR-488-5p, hsa-miR-656-3p and hsa-miR-885-5p) were screened. By intersecting 3275 predicted target genes and 925 DEGs, we finally identified 226 overlapping genes that were enriched in pathways in cancer and MAPK signaling pathway. Four hub genes (GRIA2, NRXN1, SLC6A1 and SYT1) were significantly associated with the overall survival of AT/RT patients. Candidate drugs included histone deacetylase inhibitor (givinostat), DNA synthesis inhibitor (floxuridine), cyclin-dependent kinase inhibitor (purvalanol) and janus kinase inhibitor (lestaurtinib). Conclusion In summary, this study systematically analyzed AT/RT-related miRNAs and pivotal genes to provide novel prognostic biomarkers and potential therapeutic agents.

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Zhang, Yang, et Jianguo Xu. « ATRT-03. IDENTIFICATION OF microRNA-BASED PROGNOSTIC BIOMARKERS AND CANDIDATE THERAPEUTIC AGENTS FOR ATYPICAL TERATOID/RHABDOID TUMOR ». Neuro-Oncology 22, Supplement_3 (1 décembre 2020) : iii275—iii276. http://dx.doi.org/10.1093/neuonc/noaa222.003.

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Abstract BACKGROUND MicroRNA (miRNA) has been found to be involved in development of many malignant pediatric brain tumors, including atypical teratoid/rhabdoid tumor (AT/RT) that is highly aggressive and carries a dismal prognosis. The current study investigated the potential value of miRNAs and pivotal genes associated with AT/RT using bioinformatics analysis, aiming to identify new prognostic biomarkers and candidate drugs for AT/RT patients. METHODS Differentially expressed miRNAs (DEMs) and genes (DEGs) between AT/RT and normal control samples were obtained from GEO database. The target genes of DEMs were predicted via TargetScanHuman7.2 and miRDB, and then intersected with DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of overlapping genes were conducted, followed by construction of protein-protein interaction network. Hub genes were determined by Cytoscape software, and their prognostic values were evaluated using Kaplan-Meier analysis. Connectivity Map database was used to identify latent therapeutic agents. RESULTS A total of 11 DEMs (hsa-miR-1224-5p, hsa-miR-128-3p, hsa-miR-17-5p, hsa-miR-18b-5p, hsa-miR-29c-5p, hsa-miR-329-3p, hsa-miR-379-5p, hsa-miR-433-3p, hsa-miR-488-5p, hsa-miR-656-3p and hsa-miR-885-5p) were screened. By intersecting 3275 predicted target genes and 925 DEGs, we finally identified 226 overlapping genes that were enriched in pathways in cancer and MAPK signaling pathway. Four hub genes (GRIA2, NRXN1, SLC6A1 and SYT1) were significantly associated with the overall survival of AT/RT patients. Candidate drugs included histone deacetylase inhibitor (givinostat), DNA synthesis inhibitor (floxuridine), cyclin-dependent kinase inhibitor (purvalanol) and janus kinase inhibitor (lestaurtinib). CONCLUSION In summary, this study systematically analyzed AT/RT-related miRNAs and pivotal genes to provide novel prognostic biomarkers and potential therapeutic agents.

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Kwak, Yoon Hae, Dae-Kyung Kwak, Hyun-Soo Moon, Nan Young Kim, Jae-Sung Yee et Je-Hyun Yoo. « Significant Changes in Serum MicroRNAs after High Tibial Osteotomy in Medial Compartmental Knee Osteoarthritis : Potential Prognostic Biomarkers ». Diagnostics 11, n^o 2 (7 février 2021) : 258. http://dx.doi.org/10.3390/diagnostics11020258.

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High tibial osteotomy (HTO) is an effective alternative for medial compartmental knee osteoarthritis (OA). Circulating microRNAs (miRNAs) are known to serve as OA-related biomarkers. The present study investigated the differential expression of serum miRNAs before and after HTO to identify potential miRNAs as prognostic biomarkers. miRNA-polymerase chain reaction (PCR) arrays were used to screen for miRNAs in the serum at preoperative and 6-month postoperative time points from six patients, and the differentially expressed miRNAs identified in the profiling stage were validated using real-time PCR at post-operative months 6 and 18 in 27 other HTO-treated patients. Among 84 miRNAs involved in the inflammatory process, three (miR-19b-3p, miR-29c-3p, and miR-424-5p) showed differential expression patterns in the profiling stage (p = 0.011, 0.015, and 0.021, respectively). Levels of these three and four other miRNAs (miR-140-3p, miR-454-3p, miR-let-7e-5p, and miR-885-5p) known to be related to OA progression were evaluated in the serum of 27 patients. Only four miRNAs (miR-19b-3p, miR-140-3p, miR-454-3p, and miR-let-7e-5p) were significantly upregulated at postoperative month 6 (p = 0.003, 0.005, 0.004, and 0.004, respectively), and only miR-140-3p was significantly upregulated up to 18 months after operation (p = 0.003). Together, this study reveals the significantly upregulated serum miRNAs after HTO as potential prognostic biomarkers; however, further studies are warranted to elucidate their clinical implications.

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El-Diwany, Ramy, Lisa N. Wasilewski, Kenneth W. Witwer, Justin R. Bailey, Kimberly Page, Stuart C. Ray, Andrea L. Cox, David L. Thomas et Ashwin Balagopal. « Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release ». Journal of Virology 89, n^o 18 (8 juillet 2015) : 9454–64. http://dx.doi.org/10.1128/jvi.00955-15.

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ABSTRACTPlasma microRNAs (miRNAs) change in abundance in response to disease and have been associated with liver fibrosis severity in chronic hepatitis C virus (HCV) infection. However, the early dynamics of miRNA release during acute HCV infection are poorly understood. In addition, circulating miRNA signatures have been difficult to reproduce among separate populations. We studied plasma miRNA abundance during acute HCV infection to identify an miRNA signature of early infection. We measured 754 plasma miRNAs by quantitative PCR array in a discovery cohort of 22 individuals before and during acute HCV infection and after spontaneous resolution (n= 11) or persistence (n= 11) to identify a plasma miRNA signature. The discovery cohort derived from the Baltimore Before and After Acute Study of Hepatitis. During acute HCV infection, increases in miR-122 (P< 0.01) and miR-885-5p (Pcorrected< 0.05) and a decrease in miR-494 (Pcorrected< 0.05) were observed at the earliest time points after virus detection. Changes in miR-122 and miR-885-5p were sustained in persistent (P< 0.001) but not resolved HCV infection. The circulating miRNA signature of acute HCV infection was confirmed in a separate validation cohort that was derived from the San Francisco-based You Find Out (UFO) Study (n= 28). As further confirmation, cellular changes of signature miRNAs were examined in a tissue culture model of HCV in hepatoma cells: HCV infection induced extracellular release of miR-122 and miR-885-5p despite unperturbed intracellular levels. In contrast, miR-494 accumulated intracellularly (P< 0.05). Collectively, these data are inconsistent with necrolytic release of hepatocyte miRNAs into the plasma during acute HCV infection of humans.IMPORTANCEMicroRNAs are small noncoding RNA molecules that emerging research shows can transmit regulatory signals between cells in health and disease. HCV infects 2% of humans worldwide, and chronic HCV infection is a major cause of severe liver disease. We profiled plasma miRNAs in injection drug users before, during, and (in the people with resolution) after HCV infection. We discovered miRNA signatures of acute and persistent viremia and confirmed these findings two ways: (i) in a separate cohort of people with newly acquired HCV infection and (ii) in an HCV cell culture system. Our results demonstrate that acute HCV infection induces early changes in the abundance of specific plasma miRNAs that may affect the host response to HCV infection.

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Li, Congcong, Haoyuan Han, Xiuling Li, Jiao Wu, Xinfeng Li, Hui Niu et Wantao Li. « Analysis of lncRNA, miRNA, and mRNA Expression Profiling in Type I IFN and Type II IFN Overexpressed in Porcine Alveolar Macrophages ». International Journal of Genomics 2021 (16 juin 2021) : 1–28. http://dx.doi.org/10.1155/2021/6666160.

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Current data is scarce regarding the function of noncoding RNAs (ncRNAs) such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in the interferon- (IFN-) mediated immune response. This is a comprehensive study that analyzes the lncRNA and miRNA expression profiles of the type I IFN and type II IFN in porcine alveolar macrophages using RNA sequencing. There was a total of 152 overexpressed differentially expressed (DE) lncRNAs and 21 DE miRNAs across type I IFN and type II IFN in porcine alveolar macrophages. Subsequent lncRNA-miRNA-mRNA network construction revealed the involvement of 36 DE lncRNAs and 12 DE miRNAs. LncRNAs such as the XLOC_211306, XLOC_100516, XLOC_00695, XLOC_149196, and XLOC_014459 were expressed at a higher degree in the type I IFN group, while XLOC_222640, XLOC_047290, XLOC_147777, XLOC_162298, XLOC_220210, and XLOC_165237 were expressed at a higher degree in the type II IFN group. These lncRNAs were found to act as “sponges” for miRNAs such as miR-34a, miR-328, miR-885-3p, miR-149, miR-30c-3p, miR-30b-5p, miR-708-5p, miR-193a-5p, miR-365-5p, and miR-7. Their target genes FADS2, RPS6KA1, PIM1, and NOD1 were found to be associated with several immune-related signaling pathways including the NOD-like receptor, Jak-STAT, mTOR, and PPAR signaling pathways. These experiments provide a comprehensive profile of overexpressed noncoding RNAs in porcine alveolar macrophages, providing new insights regarding the IFN-mediated immune response.

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Hussein, Neveen Abd El Moneim, Zenat A. El Kholy, Medhat M. Anwar, Mohamed A. Ahmad et Shaymaa M. Ahmad. « Plasma miR-22-3p, miR-642b-3p and miR-885-5p as diagnostic biomarkers for pancreatic cancer ». Journal of Cancer Research and Clinical Oncology 143, n^o 1 (15 septembre 2016) : 83–93. http://dx.doi.org/10.1007/s00432-016-2248-7.

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Gao, Taihong, Guangyan Gu, Jingxia Tian, Rui Zhang, Xiangrong Zheng, Yanan Wang, Qi Pang et Qian Liu. « LncRNA HSP90AA1-IT1 promotes gliomas by targeting miR-885-5p-CDK2 pathway ». Oncotarget 8, n^o 43 (8 septembre 2017) : 75284–97. http://dx.doi.org/10.18632/oncotarget.20777.

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Othumpangat, Sreekumar, Lindsley G. William, Donald H. Beezhold, Michael L. Kashon, Carmen N. Burrell, Samira Mubareka et John D. Noti. « Expression of chemokines and cytokines in influenza A and B patients have a significant correlation to the levels of serum miRNAs ». Journal of Immunology 204, n^o 1_Supplement (1 mai 2020) : 93.18. http://dx.doi.org/10.4049/jimmunol.204.supp.93.18.

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Abstract Several host cytokines display differential expression in blood plasma and serum levels during influenza virus infection. Influenza may induce a T helper 2 polarized immune response leading to the activation of cytotoxic CD8+ T cells followed by expression of interleukins (IL). MiRNAs are remarkably stable and are key regulators of mRNA transcripts for proteins. MiRNAs are involved in the regulation of influenza virus replication in many cell types. During the 2015–16 and 2016–17 influenza season, we collected blood samples from patients infected with influenza to identify the role of serum miRNAs and cytokines. In influenza B patients, 76 miRNAs were differentially expressed compared to healthy subjects (p < 0.05), while 26 exosome miRNAs were differentially expressed in influenza A patients (p < 0.05). Of these miRNAs, 11 were expressed in both influenza A and B patients. The miRNAs that were differentially regulated between influenza A and B patients included miRNA-21, miR-191-5p, miR-324-5p and miR-199a-5p. MiR-21 is reported to target IP-10. Multiplex analysis of chemokines and cytokines showed that expression of IP-10 was highest in both A and B patients. In addition, influenza A patients showed increased expression of IFNα-2, GM-CSF, IL-13, IL-17, IL-1β, IL-6 and TNF-α, while influenza B patients showed only increase in IL-1α. MiR-150-5p expression showed a high correlation with MCP-1. MiR-133a-3p potentially targets both IL-17A and IL-1b and IL-15 potentially is targeted by miR-885 and miR-122, indicating that some cytokines were targeted by more than one miRNA. Our study shows that specific circulating miRNAs may be expressed by infected lung cells and that these miRNAs may be involved in the inflammatory responses to influenza.

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McGowan, Karen, Kenneth J. Simpson et Juraj Petrik. « Expression Profiles of Exosomal MicroRNAs from HEV- and HCV-Infected Blood Donors and Patients : A Pilot Study ». Viruses 12, n^o 8 (30 juillet 2020) : 833. http://dx.doi.org/10.3390/v12080833.

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Exosomes seem to play an important role in hepatits C virus (HCV) and hepatitis E virus (HEV) infection by shielding their cargo from the host immune responses, with microRNAs being key exosomal components. Little is known about their involvement in a mixed HCV/HEV infection or at the early stages of infection, such as in asymptomatic blood donors (BDs). To obtain preliminary data, we have compared the exosomal microRNA expression profiles in four each of HCV RNA-positive, HEV RNA-positive and negative blood donors and four patients, one of whom was a rare patient with HCV/HEV co-infection. Exosomes were purified from sera by a combination of a precipitation and density gradient centrifugation and exosomal microRNA was analysed using Taqman array cards. Out of 33 deregulated miRNAs, miR-885-5p and miR-365 were upregulated in HCV BDs, miR-627-5p was downregulated in HCV BD and miR-221 was downregulated in HCV patients and BDs. In HEV infection, miR-526b appeared specifically downregulated. Six miRNAs (miR-628-3p, miR-194, miR-151-3p, miR-512-3p, miR-335 and miR-590) indicated a potential involvement in both infections. First time preliminary data on pre- and post-antiviral treatment exosomal microRNA profiles of the HEV/HCV co-infected patient revealed a pool of 77 upregulated and 43 downregulated miRNAs to be further investigated for their potential roles in these viral infections.

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Othumpangat, Sreekumar, William G. Lindsley, Donald H. Beezhold, Michael L. Kashon, Carmen N. Burrell, Samira Mubareka et John D. Noti. « Differential Expression of Serum Exosome microRNAs and Cytokines in Influenza A and B Patients Collected in the 2016 and 2017 Influenza Seasons ». Pathogens 10, n^o 2 (2 février 2021) : 149. http://dx.doi.org/10.3390/pathogens10020149.

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MicroRNAs (miRNAs) have remarkable stability and are key regulators of mRNA transcripts for several essential proteins required for the survival of cells and replication of the virus. Exosomes are thought to play an essential role in intercellular communications by transporting proteins and miRNAs, making them ideal in the search for biomarkers. Evidence suggests that miRNAs are involved in the regulation of influenza virus replication in many cell types. During the 2016 and 2017 influenza season, we collected blood samples from 54 patients infected with influenza and from 30 healthy volunteers to identify the potential role of circulating serum miRNAs and cytokines in influenza infection. Data comparing the exosomal miRNAs in patients with influenza B to healthy volunteers showed 76 miRNAs that were differentially expressed (p < 0.05). In contrast, 26 miRNAs were differentially expressed between patients with influenza A (p < 0.05) and the controls. Of these miRNAs, 11 were commonly expressed in both the influenza A and B patients. Interferon (IFN)-inducing protein 10 (IP-10), which is involved in IFN synthesis during influenza infection, showed the highest level of expression in both influenza A and B patients. Influenza A patients showed increased expression of IFNα, GM-CSF, interleukin (IL)-13, IL-17A, IL-1β, IL-6 and TNFα, while influenza B induced increased levels of EGF, G-CSF, IL-1α, MIP-1α, and TNF-β. In addition, hsa-miR-326, hsa-miR-15b-5p, hsa-miR-885, hsa-miR-122-5p, hsa-miR-133a-3p, and hsa-miR-150-5p showed high correlations to IL-6, IL-15, IL-17A, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) with both strains of influenza. Next-generation sequencing studies of H1N1-infected human lung small airway epithelial cells also showed similar pattern of expression of miR-375-5p, miR-143-3p, 199a-3p, and miR-199a-5p compared to influenza A patients. In summary, this study provides insights into the miRNA profiling in both influenza A and B virus in circulation and a novel approach to identify the early infections through a combination of cytokines and miRNA expression.

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Zhang, Zhuhong, Jing Yin, Jian Yang, Wenzhi Shen, Chunyan Zhang, Wenjun Mou, Jinhua Luo et al. « miR-885-5p suppresses hepatocellular carcinoma metastasis and inhibits Wnt/β-catenin signaling pathway ». Oncotarget 7, n^o 46 (12 octobre 2016) : 75038–51. http://dx.doi.org/10.18632/oncotarget.12602.

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Sandrim, VC, MR Luizon, AC Palei, JE Tanus-Santos et RC Cavalli. « Circulating microRNA expression profiles in pre-eclampsia : evidence of increased miR-885-5p levels ». BJOG : An International Journal of Obstetrics & ; Gynaecology 123, n^o 13 (8 février 2016) : 2120–28. http://dx.doi.org/10.1111/1471-0528.13903.

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Xu, Fei, Jing-Jun Yan, Yun Gan, Ying Chang, Hong-Ling Wang, Xing-Xing He et Qiu Zhao. « miR-885-5p Negatively Regulates Warburg Effect by Silencing Hexokinase 2 in Liver Cancer ». Molecular Therapy - Nucleic Acids 18 (décembre 2019) : 308–19. http://dx.doi.org/10.1016/j.omtn.2019.09.002.

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Jiang, Zhaoyu, Huaiping Cui, Shujie Zeng et Leping Li. « miR-885-5p Inhibits Invasion and Metastasis in Gastric Cancer by Targeting Malic Enzyme 1 ». DNA and Cell Biology 40, n^o 5 (1 mai 2021) : 694–705. http://dx.doi.org/10.1089/dna.2020.6478.

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Afanasyeva, E. A., P. Mestdagh, C. Kumps, J. Vandesompele, V. Ehemann, J. Theissen, M. Fischer et al. « MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival ». Cell Death & ; Differentiation 18, n^o 6 (14 janvier 2011) : 974–84. http://dx.doi.org/10.1038/cdd.2010.164.

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Xu, Fei, Jing-Jun Yan, Yun Gan, Yupeng Zhang, Xingxing He et Qiu Zhao. « 681 – Mir-885-5P Negatively Regulates Warburg Effect by Silencing Hexokinase 2 in Liver Cancer ». Gastroenterology 156, n^o 6 (mai 2019) : S—1209. http://dx.doi.org/10.1016/s0016-5085(19)40007-3.

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Nasser, Mona Zaky, Naglaa Ali Zayed, Ahmed Mahmoud Mohamed, Dina Attia, Gamal Esmat et Ahmed Khairy. « Circulating microRNAs (miR-21, miR-223, miR-885-5p) along the clinical spectrum of HCV-related chronic liver disease in Egyptian patients ». Arab Journal of Gastroenterology 20, n^o 4 (décembre 2019) : 198–204. http://dx.doi.org/10.1016/j.ajg.2019.11.003.

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Parray, Aijaz, Fayaz Ahmad Mir, Asmma Doudin, Ahmad Iskandarani, Ibn Mohammed Masud Danjuma, Rahim Ayadathil Thazhhe Kuni, Alaaedin Abdelmajid et al. « SnoRNAs and miRNAs Networks Underlying COVID-19 Disease Severity ». Vaccines 9, n^o 10 (23 septembre 2021) : 1056. http://dx.doi.org/10.3390/vaccines9101056.

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There is a lack of predictive markers for early and rapid identification of disease progression in COVID-19 patients. Our study aims at identifying microRNAs (miRNAs)/small nucleolar RNAs (snoRNAs) as potential biomarkers of COVID-19 severity. Using differential expression analysis of microarray data (n = 29), we identified hsa-miR-1246, ACA40, hsa-miR-4532, hsa-miR-145-5p, and ACA18 as the top five differentially expressed transcripts in severe versus asymptomatic, and ACA40, hsa-miR-3609, ENSG00000212378 (SNORD78), hsa-miR-1231, hsa-miR-885-3p as the most significant five in severe versus mild cases. Moreover, we found that white blood cell (WBC) count, absolute neutrophil count (ANC), neutrophil (%), lymphocyte (%), red blood cell (RBC) count, hemoglobin, hematocrit, D-Dimer, and albumin are significantly correlated with the identified differentially expressed miRNAs and snoRNAs. We report a unique miRNA and snoRNA profile that is associated with a higher risk of severity in a cohort of SARS-CoV-2 infected patients. Altogether, we present a differential expression analysis of COVID-19-associated microRNA (miRNA)/small nucleolar RNA (snoRNA) signature, highlighting their importance in SARS-CoV-2 infection.

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Meier, Claudia, Philip Hardtstock, Sophie Joost, Vijay Alla et Brigitte M. Pützer. « p73 and IGF1R Regulate Emergence of Aggressive Cancer Stem–like Features via miR-885-5p Control ». Cancer Research 76, n^o 2 (10 novembre 2015) : 197–205. http://dx.doi.org/10.1158/0008-5472.can-15-1228.

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Lixin, Sun, Sun Wei, Song Haibin, Lang Qingfu et Pei Tiemin. « miR‐885‐5p inhibits proliferation and metastasis by targeting IGF2BP1 and GALNT3 in human intrahepatic cholangiocarcinoma ». Molecular Carcinogenesis 59, n^o 12 (14 octobre 2020) : 1371–81. http://dx.doi.org/10.1002/mc.23262.

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Bento, Leyre, Teresa Ros, Josep Muncunill, Víctor Asensio, Concepción Fernández, Adriana Marcela Quintero, Adriana Sas et al. « Analysis of Micro-RNAs Associated to Treatment Failure in Diffuse Large B Cell Lymphoma ». Blood 134, Supplement_1 (13 novembre 2019) : 1627. http://dx.doi.org/10.1182/blood-2019-130544.

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Introduction: Micro-RNAs (miRNAs) are 19-24 nucleotide non-coding RNAs that regulate gene expression through the inactivation of their messenger RNA. Previous studies have demonstrated the important role of some miRNAs in the development of cancer. Specifically, in diffuse large B cell lymphoma (DLBCL), miRNAs involved in lymphomagenesis were identified but understanding their biological function continues to be a challenge. Nevertheless, the pathogenesis effects of some miRNAs such as miR-125a, miR-17-92 cluster or mi-R-155 are well characterized. Some studies suggest that miRNAs also possess a prognostic potential role in DLBCL. For this reason, our objective was to analyze the different miRNAs involved in the chemo-sensitivity or resistance to the first line treatment, their correlation with standard prognostic factors at diagnosis and the role of these miRNAs in survival in patients with DLBCL. Material and methods: Patients homogeneously treated with R-CHOP from 1999-2013 were reviewed from 3 Spanish centers. They were retrospectively obtained from Pathology Department registry to avoid selection bias. We included those patients with valid genomic material in formalin-fixed-paraffin-embedded tissue and with available clinical data. Samples were processed using the miRNA 4 Affymetrix microarrays kit in a discovery group that included 2 cohorts (patients with durable complete remission (CR) versus refractory or early relapsing patients). Those miRNAs with differential expression were validated in the whole series with quantitative RT-PCR. We also analyzed the role of these miRNAs as predictors of event-free survival (EFS) and overall survival (OS) and their relationship with standard prognostic factors in DLBCL. Results: We identified 156 patients homogeneously treated with R-CHOP. Finally, 96 samples were obtained with valid material for RNA extraction. To identify those miRNAs with prognostic implication, a discovery cohort of 12 patients was used in which all the cases had poor prognosis with high tumor load and advance disease (III-IV stage and unfavorable R-IPI). On this basis of poor prognosis, 2 groups were defined totally opposed from the point of view of the treatment response and evolution: chemo-resistance group (n=6) including refractory or relapsed (RR) patients (first 12 months) and chemo-sensitive group (n=6) including patients with at least 3 years of CR. A hierarchical clustering was performed in which 26 miRNAs differentially expressed were identified. A screening of miRNAs was carried out based on the fold-change and pathways involved and finally we obtained 10 miRNAs differentially expressed in RR group. The validation of these miRNAs was performed with quantitative RT-PCR in the whole series which finally included 68 samples with valid material. A univariate survival analysis including clinical prognostic factors and the selected 10 miRNAs was performed. We confirmed that 7 of them (miR-20b-5p, miR-1244, miR-6840-3p, miR-1231, miR-193b-5p, miR-6860-5p y miR-199a-5p) significantly influenced EFS and 6 of them (miR-1244, miR-1231, miR-193b-5p, miR-885-3p, miR-182-5p y miR-199a-5p) on OS. From these 10 miRNAs, only 3 had a significant prognosis role not only for EFS but also for OS and progression-free survival (PFS): miR-1244, miR-193b-5p and miR-1231. The overexpression of miR-1244 and miR-193-5p were associated with advance stage and worse clinical prognosis factors (p<0.05). A multivariate analysis was performed including clinical and biological variables and we obtained that the overexpression of miR-1231, high R-IPI and a reduction of relative dose intensity (RDI) >15% were independently associated with worse SG and EFS (Figure 1). In previously reported studies, these 3 miRNAs have been related with proliferative events such as the overexpression of myc or anti-apoptosis. Also, the miR-1231 may be related with new lymphomagenesis pathways associated to viral infections. Conclusions: Through a discovery group focused on progression/refractoriness, a group of new miRNAs differentially expressed on chemo-resistant patients with DLBCL was identified. The overexpression of miR-1244 and miR-193-5p was associated with more extensive disease and worse clinical prognostic factors. The high R-IPI, reduction of >15% RDI and the overexpression of miR-1231 were independently associated with worse EFS and OS. Disclosures Sánchez-González: Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Salar:Roche: Research Funding, Speakers Bureau; Janssen Pharmaceuticals: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy.

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Lobo, João, Ad J. M. Gillis, Annette van den Berg, Lambert C. J. Dorssers, Gafanzer Belge, Klaus-Peter Dieckmann, Henk P. Roest et al. « Identification and Validation Model for Informative Liquid Biopsy-Based microRNA Biomarkers : Insights from Germ Cell Tumor In Vitro, In Vivo and Patient-Derived Data ». Cells 8, n^o 12 (14 décembre 2019) : 1637. http://dx.doi.org/10.3390/cells8121637.

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Liquid biopsy-based biomarkers, such as microRNAs, represent valuable tools for patient management, but often do not make it to integration in the clinic. We aim to explore issues impeding this transition, in the setting of germ cell tumors, for which novel biomarkers are needed. We describe a model for identifying and validating clinically relevant microRNAs for germ cell tumor patients, using both in vitro, in vivo (mouse model) and patient-derived data. Initial wide screening of candidate microRNAs is performed, followed by targeted profiling of potentially relevant biomarkers. We demonstrate the relevance of appropriate (negative) controls, experimental conditions (proliferation), and issues related to sample origin (serum, plasma, cerebral spinal fluid) and pre-analytical variables (hemolysis, contaminants, temperature), all of which could interfere with liquid biopsy-based studies and their conclusions. Finally, we show the value of our identification model in a specific scenario, contradicting the presumed role of miR-375 as marker of teratoma histology in liquid biopsy setting. Our findings indicate other putative microRNAs (miR-885-5p, miR-448 and miR-197-3p) fulfilling this clinical need. The identification model is informative to identify the best candidate microRNAs to pursue in a clinical setting.

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Ju, Yeongdon, Young Mi Seol, Jungho Kim, Hyunwoo Jin, Go-Eun Choi et Aelee Jang. « Expression Profiles of Circulating MicroRNAs in XELOX-Chemotherapy-Induced Peripheral Neuropathy in Patients with Advanced Gastric Cancer ». International Journal of Molecular Sciences 23, n^o 11 (27 mai 2022) : 6041. http://dx.doi.org/10.3390/ijms23116041.

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Gastric cancer (GC) is one of the most common cancers and a leading cause of cancer deaths around the world. Chemotherapy is one of the most effective treatments for cancer patients, and has remarkably enhanced survival rates. However, it has many side effects. Recently, microRNAs (miRNAs) have been intensively studied as potential biomarkers for cancer diagnosis and treatment monitoring. However, definitive biomarkers in chemotherapy-induced peripheral neuropathy (CIPN) are still lacking. The aim of this study was to identify the factors significant for neurological adverse events in GC patients receiving XELOX (oxaliplatin and capecitabine) chemotherapy. The results show that XELOX chemotherapy induces changes in the expression of hsa-miR-200c-3p, hsa-miR-885-5p, and hsa-miR-378f. Validation by qRT-PCR demonstrated that hsa-miR-378f was significantly downregulated in CIPN. Hsa-miR-378f was identified as showing a statistically significant correlation in GC patients receiving XELOX chemotherapy according to the analysis of differentially expressed (DE) miRNAs. Furthermore, 34 potential target genes were predicted using a web-based database for miRNA target prognostication and functional annotations. The identified genes are related to the peptidyl-serine phosphorylation and regulation of alternative mRNA splicing with enrichment in the gastric cancer, neurotrophin, MAPK, and AMPK signaling pathways. Collectively, these results provide information useful for developing promising strategies for the treatment of XELOX-chemotherapy-induced peripheral neuropathy.

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Yao, Dayong, Shunyao Xia, Chengjun Jin, Weiming Zhao, Wenjia Lan, Zan Liu et Youcheng Xiu. « Feedback activation of GATA1/miR-885-5p/PLIN3 pathway decreases sunitinib sensitivity in clear cell renal cell carcinoma ». Cell Cycle 19, n^o 17 (12 août 2020) : 2195–206. http://dx.doi.org/10.1080/15384101.2020.1801189.

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Zou, Shubiao, Yao Rao et Weicai Chen. « miR‐885‐5p plays an accomplice role in liver cancer by instigating TIGAR expression via targeting its promoter ». Biotechnology and Applied Biochemistry 66, n^o 5 (27 août 2019) : 763–71. http://dx.doi.org/10.1002/bab.1767.

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Duan, Jinlong, Yuefen Pan, Xi Yang, Liping Zhong, Yin Jin, Jiamin Xu, Jing Zhuang et Shuwen Han. « Screening of T Cell-Related Long Noncoding RNA-MicroRNA-mRNA Regulatory Networks in Non-Small-Cell Lung Cancer ». BioMed Research International 2020 (14 novembre 2020) : 1–13. http://dx.doi.org/10.1155/2020/5816763.

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Background. Lung cancer (LC) has the highest mortality rate among all the other types of cancer in the world. T cells are known to be the key factor in inducing the immune response during LC. Objective. In this study, we aimed to screen and analyze RNAs associated with CD8(+) T cells and activated memory CD4(+) T cells in lung adenocarcinomas, a subtype of non-small-cell lung cancer (NSCLC-LUAD). Methods. Gene expression RNA-seq data and clinical data of NSCLC-LUAD were downloaded from the XENA database. The data were divided into low scores and high scores based on the Stromal and Immune scores. Then, all the genes were screened for identifying those specifically associated with CD8(+) T cells and activated memory CD4(+) T cells. The screened genes were used for the construction of the protein-protein interaction (PPI) network and for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis along with prognosis analysis. Based on the results of the prognostic analysis, the prognostic-related genes were used to analyze long noncoding (lnc)RNA-micro(mi)RNA-mRNA networks and to predict small chemical molecules. Results. According to the Immune and Stromal scores, a total of 885 upregulated and 29 downregulated RNAs were identified. A total of 90 differentially expressed genes (DEGs) were found to be related to CD8(+) T immune cells, and 48 DEGs were related to activated memory CD4(+) T cells. GPR174 and CD226 suggested a favorable prognosis. For CD8(+) and activated memory CD4(+) T cells, 112 and 113 PPI edges were obtained, respectively. GPR174 was found to be regulated by hsa-miR-19b-5p and hsa-miR-19b-2-5p, and both of these two miRNAs were regulated by lncRNA PCED1B-AS1. CD226 was regulated by hsa-miR-379-5p, which was in turn regulated by lncRNA RP11-81H14.2. Conclusion. Our findings provide a deeper understanding of the T cell-related ceRNA regulatory mechanism in NSCLC-LUAD pathogenesis.

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de Cubas, Aguirre A., L. Javier Leandro-García, Francesca Schiavi, Veronika Mancikova, Iñaki Comino-Méndez, Lucía Inglada-Pérez, Manuel Perez-Martinez et al. « Integrative analysis of miRNA and mRNA expression profiles in pheochromocytoma and paraganglioma identifies genotype-specific markers and potentially regulated pathways ». Endocrine-Related Cancer 20, n^o 4 (9 mai 2013) : 477–93. http://dx.doi.org/10.1530/erc-12-0183.

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Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine neoplasias of neural crest origin that can be part of several inherited syndromes. Although their mRNA profiles are known to depend on genetic background, a number of questions related to tumor biology and clinical behavior remain unanswered. As microRNAs (miRNAs) are key players in the modulation of gene expression, their comprehensive analysis could resolve some of these issues. Through characterization of miRNA profiles in 69 frozen tumors with germline mutations in the genes SDHD, SDHB, VHL, RET, NF1, TMEM127, and MAX, we identified miRNA signatures specific to, as well as common among, the genetic groups of PCCs/PGLs. miRNA expression profiles were validated in an independent series of 30 composed of VHL-, SDHB-, SDHD-, and RET-related formalin-fixed paraffin-embedded PCC/PGL samples using quantitative real-time PCR. Upregulation of miR-210 in VHL- and SDHB-related PCCs/PGLs was verified, while miR-137 and miR-382 were confirmed as generally upregulated in PCCs/PGLs (except in MAX-related tumors). Also, we confirmed overexpression of miR-133b as VHL-specific miRNAs, miR-488 and miR-885-5p as RET-specific miRNAs, and miR-183 and miR-96 as SDHB-specific miRNAs. To determine the potential roles miRNAs play in PCC/PGL pathogenesis, we performed bioinformatic integration and pathway analysis using matched mRNA profiling data that indicated a common enrichment of pathways associated with neuronal and neuroendocrine-like differentiation. We demonstrated that miR-183 and/or miR-96 impede NGF-induced differentiation in PC12 cells. Finally, global proteomic analysis in SDHB and MAX tumors allowed us to determine that miRNA regulation occurs primarily through mRNA degradation in PCCs/PGLs, which partially confirmed our miRNA–mRNA integration results.

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Wang, Kai. « Serum miR-885-5p can be used as a marker for efficacy prediction and prognosis of advanced liver cancer ». Cellular and Molecular Biology 66, n^o 6 (30 septembre 2020) : 135. http://dx.doi.org/10.14715/cmb/2020.66.6.24.

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Jin, Xiaoyan, Zhengyi Wang, Wenyang Pang, Jian Zhou, Yong Liang, Jingjin Yang, Linjun Yang et Qiang Zhang. « Upregulated hsa_circ_0004458 Contributes to Progression of Papillary Thyroid Carcinoma by Inhibition of miR-885-5p and Activation of RAC1 ». Medical Science Monitor 24 (7 août 2018) : 5488–500. http://dx.doi.org/10.12659/msm.911095.

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Liang, Xiaolong, Chuan Qin, Gangfeng Yu, Xiong Guo, Anqi Cheng, Han Zhang et Ziwei Wang. « Circular RNA circRAB31 acts as a miR-885-5p sponge to suppress gastric cancer progression via the PTEN/PI3K/AKT pathway ». Molecular Therapy - Oncolytics 23 (décembre 2021) : 501–14. http://dx.doi.org/10.1016/j.omto.2021.11.002.

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Guan, Xiaoxiang, Zhensheng Liu, Hongliang Liu, Hongping Yu, Li‐E Wang, Erich M. Sturgis, Guojun Li et Qingyi Wei. « A functional variant at the miR‐885‐5p binding site of CASP3 confers risk of both index and second primary malignancies in patients with head and neck cancer ». FASEB Journal 27, n^o 4 (27 décembre 2012) : 1404–12. http://dx.doi.org/10.1096/fj.12-223420.

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Fernandez de Larrea, Carlos, Tania Diaz, Alfons Navarro, Ester Lozano, Mari-Pau Mena, Ignacio Isola, Natalia Tovar, Maria Teresa Cibeira, Laura Rosinol et Joan Bladé. « Mir-485-3p and Mir-654-3p Expression in Bone Marrow Mesenchymal Stromal Cells in Patients with Monoclonal Gammopathies Is Related to the Status of the Disease ». Blood 132, Supplement 1 (29 novembre 2018) : 3155. http://dx.doi.org/10.1182/blood-2018-99-112222.

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Abstract Background: Crosstalk between malignant plasma cells and surrounding cells in the bone marrow (BM), such as mesenchymal stromal cells (MSCs), endothelial cells and immune cells, is crucial for pathogenesis of multiple myeloma (MM) and in asymptomatic monoclonal gammopathies. In these diseases, microRNAs (miRNAs) could be useful as biomarkers for diagnosis, prognosis and evaluation of treatment response. miRNAs can be released to the serum and transferred among MM cells and BM-MSCs as cell-cell communication. Previously, we have showed a serum 14-miRNA signature associated with complete remission (CR) after autologous stem-cell transplantation (ASCT). In this sense, patients in CR with partial recovery of two normal serum miRNA levels, similar to those with monoclonal gammopathy of undetermined significance (MGUS), was associated with better prognosis. The aim of this study was to analyze the miRNAs profile in mesenchymal stromal cells derived from bone marrow of patients with multiple myeloma in different status of the disease, comparing with MGUS controls. Methods: We analyzed samples from 95 patients with MGUS (N=23), MM at diagnosis (N=14), relapsed/refractory MM (N=14), MM in partial response (PR) or very good partial response (VGPR) (N=15), MM in CR (N=24) and healthy donors (N=5). Mononuclear cells from BM samples were cultured in DMEM containing 10% FBS. After a week, non-adherent cells were removed, whereas BM-MSCs were selected by their adherence to the plastic and their phenotype was confirmed by multiparametric flow cytometry. In a first screening phase, we analyzed 670 microRNAs in 20 primary BM-MSC from patients with MGUS (N=4), symptomatic MM (N=8) and MM in CR (N=8). miRNAs differentially expressed were identified according to a supervised analysis using significance analysis of microarrays (SAM) and Student's t-test based on multivariate permutation (with random variance model). miRNAs differentially expressed between groups of patients were validated in the whole cohort of BM-MSC from patients. Paired malignant plasma cells (CD38+) miRNA expression from patients with symptomatic MM as well as miRNA in serum samples paired with BM-MSC samples were also compared. RmiR package was used to identify miRNA targets, cross-correlating the miRNA expression data from the present study with our findings on the gene expression signature (Affymetrix Human Genome U219 array) in 12 BM-MSCs from patients (4 MGUS, 4 symptomatic MM and 4 in CR), based on the predicted targets from TargetScan and miRBase databases. Results: In the screening phase, we identified a miRNA profile of 10 miRNAs (miR-663b, miR-654-3p, miR-206, miR-411*, miR-885-5p, miR-668, miR-638, miR-485-3p, miR-744* and miR-199a) differentially expressed between patients with symptomatic MM and MM in CR (adjusted p-value <0.0001). In the validation phase, miR-485-3p and miR-654-3p resulted differentially expressed in the three groups of patients: MGUS, symptomatic MM and patients in CR (ANOVA test: p=0.0101 and p=0.0228, respectively). The levels of these miRNAs were significantly decreased in patients with MM than in those with MGUS, and these levels seemed to recover when patients achieved CR. These two miRNAs (miR-485-3p and miR-654-3p) were also correlated with all degrees of response in MM and with asymptomatic gammopathies (ANOVA test: p=0.0154 and p=0.0487, respectively). Moreover, paired cross-correlation among these two miRNAs expression with our results in mRNA gene expression profile data showed 324 for miR-485-3p and 265 for miR-654-3p genes (correlation index < -0.8) (Figure 1A and 1B). miR-485-3p and miR-654-3p showed a higher expression in BM-MSC than in MM CD38+ cells, suggesting MSC as cell of origin for these miRNAs. Serum expression of these two miRNAs was concordant with the observed in BM-MSC, with higher in patients in CR and MGUS than in those with symptomatic MM (Figure 1C and 1D). miRNA expression in BM-MSC supernatant as well as the identification of the biological role and validation of the miRNA targets are ongoing. Conclusion: miR-485-3p and miR-654-3p expression in mesenchymal stromal cells from bone marrow in patients with multiple myeloma and asymptomatic monoclonal gammopathies is related to the status of the disease and the response to treatment. These miRNAs are also expressed in serum, resulting in potential biomarkers for disease activity and risk of progression. Disclosures Rosinol: Janssen, Celgene, Amgen, Takeda: Honoraria. Bladé:Janssen: Honoraria.

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Yang, Zhi, Fan Zhang, Kai Cai et Jianxin Xu. « LncRNA HOXA-AS2 facilitates prostate cancer progression by inhibiting miR-885-5p to upregulate KDM5B ». Kidney and Blood Pressure Research, 18 novembre 2022. http://dx.doi.org/10.1159/000527140.

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Background: The regulatory network of competing endogenous RNAs (ceRNAs) affects tumorigenesis. In this study, we aimed to investigate the mechanism by which long non-coding RNA (lncRNA) HOXA-AS2 promotes prostate cancer (PCa) progression. Methods: The expression levels of HOXA-AS2, miR-885-5p, and KDM5B in PCa tissues and cell lines were evaluated by qRT-PCR or western blotting. CCK-8 assay, caspase-3 activity assay, flow cytometry, and scratch test revealed changes in cell proliferation, caspase-3 activity, apoptosis, and migration, respectively. Luciferase and radioimmunoprecipitation assays were used to evaluate the correlation among HOXA-AS2, miR-885-5p, and KDM5B expression profiles. Results: HOXA-AS2 expression level was elevated in PCa tissues and cells. Silencing of HOXA-AS2 suppressed proliferation and migration and facilitated apoptosis in PCa cells. HOXA-AS2 competitively adsorbed miR-885-5p, thereby blocking the effect of HOXA-AS2 knockdown by the miR-885-5p inhibitor in PCa cells. Moreover, KDM5B, a target of miR-885-5p, neutralized the function of miR-885-5p in PCa cells. Conclusions: This study revealed a potential ceRNA regulatory pathway in which HOXA-AS2 affects KDM5B expression levels by sponging miR-885-5p to promote PCa development and progression.

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Guo, Xiongbo, et Wenbiao Zhu. « Arsenic Trioxide Affects the Proliferation of Gastric Cancer Cells through MiR-885-5p/CDC73 Axis ». Iranian Journal of Public Health, 14 janvier 2023. http://dx.doi.org/10.18502/ijph.v52i1.11674.

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Background: To explore Arsenic trioxide (As2O3) and its regulated miR-885-5p/CDC73 signaling pathway involved in the development of gastric cancer. Methods: Fifty-two healthy patients and patients with gastric cancer were enrolled 2019-2020 in He Xian Memorial Hospital, Guangzhou, China. The patients with gastric cancer were divided into control group and As2O3 administration group. After 2 courses of treatment, their peripheral blood was collected to analyze the therapeutic effect. miR-885-5p expression in peripheral blood was analyzed by qRT-PCR. As2O3 was added into MGC-803 gastric cancer cell line at 0, 10, 20, 40 and 80 μmol/L. The proliferation rate and 48h IC50 value of gastric cancer cells were investigated by CCK-8, and the effect of As2O3 on miR-885-5p expression in the cells was analyzed. Results: After 4 weeks of treatment, the objective efficiency of control group and As2O3 administration group was 17.3% and 13.4%, respectively, without significant statistical difference. The overall benefit rate of As2O3 administration group was significantly higher than that of the normal treatment group (P=0.049). qRT-PCR experiment results found that miR-885-5p significantly highly expressed in peripheral blood in the As2O3 administration group, while miR-885-5p in gastric cancer was lower compared with normal people. Adding As2O3 to the gastric cancer cells could significantly inhibit miR-885-5p expression, while miR-885-5p in gastric cancer cells affected cell expression by targeted regulation, affecting cell proliferation. Conclusion: As2O3 may be used as a drug treatment program for gastric cancer, and mainly regulates the proliferation of gastric cancer cells by affecting the miR-885-5p/CDC73 target axis to participate in the development of gastric cancer.

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Shou, Jixin, Haidong Gao, Sen Cheng, Bingbing Wang et Haibo Guan. « LncRNA HOXA-AS2 promotes glioblastoma carcinogenesis by targeting miR-885-5p/RBBP4 axis ». Cancer Cell International 21, n^o 1 (11 janvier 2021). http://dx.doi.org/10.1186/s12935-020-01690-1.

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Abstract Background LncRNA HOXA-AS2 has been found in the literature to deteriorate glioblastoma. However, its regulatory mechanism is yet to be fully investigated. Our study focused chiefly on the interaction and role of the HOXA-AS2/miR-885-5p/RBBP4 axis in the development of glioblastoma. Methods qRT-PCR analysis was performed to detect the expression of lncRNA, miRNA and mRNA in glioblastoma tissues and cells. Dual-luciferase assay, RIP assay and RNA pull-down assay were later carried out to reveal the interactions among HOXA-AS2, miR-885-5p and RBBP4. After that, CCK-8 assay, BrdU assay, nude mice xenografting assay, western blot assay, and flow cytometry were carried out to analyze the effect of the HOXA-AS2/miR-885-5p/RBBP4 axis on glioblastoma samples. Results HOXA-AS2 and RBBP4 were found to be overexpressed in glioblastoma. Experimental results showed that HOXA-AS2 and RBBP4 contributed to the tumorigenesis of glioblastoma cells. However, miR-885-5p was observed to be downregulated in glioblastoma. Findings also indicated that HOXA-AS2 could negatively regulate miR-885-5p, thereby enhancing RBBP4 expression. Conclusion Overall, HOXA-AS2 promoted the tumorigenesis of glioblastoma by targeting and regulating miR-885-5p to induce the expression of RBBP4.

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Tu, Guo-wei, Jie-fei Ma, Jia-kun Li, Ying Su, Jing-chao Luo, Guang-wei Hao, Ming-hao Luo, Yi-rui Cao, Yi Zhang et Zhe Luo. « Exosome-Derived From Sepsis Patients' Blood Promoted Pyroptosis of Cardiomyocytes by Regulating miR-885-5p/HMBOX1 ». Frontiers in Cardiovascular Medicine 9 (8 mars 2022). http://dx.doi.org/10.3389/fcvm.2022.774193.

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BackgroundSeptic myocardial depression has been associated with increased morbidity and mortality. miR-885-5p has been shown to regulate cell growth, senescence, and/or apoptosis. Published studies demonstrated that Homeobox-containing protein 1 (HMBOX1) inhibits inflammatory response, regulates cell autophagy, and apoptosis. However, the role of miR-885-5p/HMBOX1 in sepsis and septic myocardial depression and the underlying mechanism is not fully understood.Materials and MethodsExosomes (exos) derived from sepsis patients (sepsis-exos) were isolated using ultracentrifugation. Rats were subjected to cecal ligation and puncture surgery and treated with sepsis-exos. HMBOX1 was knocked down or overexpressed in AC16 cells using lentiviral plasmids carrying short interfering RNAs targeting human HMBOX1 or carrying HMBOX1 cDNA. Cell pyroptosis was measured by flow cytometry. The secretion of IL-1β and IL-18 was examined by ELISA kits. Quantitative polymerase chain reaction (PCR) or western blot was used for gene expression.ResultsSepsis-exos increased the level of miR-885-5p, decreased HMBOX1, elevated IL-1β and IL-18, and promoted pyroptosis in AC16 cells. Septic rats treated with sepsis-exos increased the serum inflammatory cytokines is associated with increased pyroptosis-related proteins of hearts. MiR-885-5p bound to the three prime untranslated regions of HMBOX1 to negatively regulate its expression. Overexpressing HMBOX1 reversed miR-885-5p-induced elevation of inflammatory cytokines and upregulation of NLRP3, caspase-1, and GSDMD-N in AC16 cells. The mechanistic study indicated that the effect of HMBOX1 was NF-κB dependent.ConclusionSepsis-exos promoted the pyroptosis of AC16 cells through miR-885-5p via HMBOX1. The results show the significance of the miR-885-5p/HMBOX1 axis in myocardial cell pyroptosis and provide new directions for the treatment of septic myocardial depression.

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« Epigenetic Modulation in Viral Hepatitis C Infected Patients after Successful Therapy ». Biointerface Research in Applied Chemistry 13, n^o 3 (5 juin 2022) : 213. http://dx.doi.org/10.33263/briac133.213.

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Nowadays, hepatitis C-virus (HCV) represents a challenging liver condition for infected patients and health care systems worldwide. Thus, identifying new biomarkers for early diagnosis and therapy response prediction should be prioritized. Our study aims to identify new epigenetic markers in patients with HCV infection before and after successful direct-acting agents therapy (DAA) and correlate them with standard diagnostic tools. We analyzed blood samples from 12 healthy volunteers and 22 HCV infected patients, before and 3 months after DAA, by assessing: liver transaminases, alpha-fetoprotein, cryoglobulinemia, miR-7-1-3p, miR-21-3p, miR122-5p, miR-885-5p, miR-16-5p, and liver fibrosis (FibroScan®). The study groups were Ctrl (Control group), HCV (HCV infected patients before therapy), and SVR (sustained viral response group). miR-7-1-3p was up-regulated in SVR compared to HCV. No difference was observed between Ctrl and HCV. MiR-21-3p was up-regulated in SVR compared to Ctrl. MiR-122-5p was up-regulated in both, HCV and SVR groups, while miR-885-5p was up-regulated in HCV and down-regulated in SVR group. Moreover, miR-122-5p and miR-885-5p were correlated with liver cytolysis. Our results revealed an innovative panel of epigenetic biomarkers in the early stage of HCV infection and its variation after successful DAA therapy.

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Streese, Lukas, Philippe Demougin, Paula Iborra, Alexander Kanitz, Arne Deiseroth, Julia M. Kröpfl, Arno Schmidt-Trucksäss, Mihaela Zavolan et Henner Hanssen. « Untargeted sequencing of circulating microRNAs in a healthy and diseased older population ». Scientific Reports 12, n^o 1 (22 février 2022). http://dx.doi.org/10.1038/s41598-022-06956-4.

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AbstractWe performed untargeted profiling of circulating microRNAs (miRNAs) in a well characterized cohort of older adults to verify associations of health and disease-related biomarkers with systemic miRNA expression. Differential expression analysis revealed 30 miRNAs that significantly differed between healthy active, healthy sedentary and sedentary cardiovascular risk patients. Increased expression of miRNAs miR-193b-5p, miR-122-5p, miR-885-3p, miR-193a-5p, miR-34a-5p, miR-505-3p, miR-194-5p, miR-27b-3p, miR-885-5p, miR-23b-5b, miR-365a-3p, miR-365b-3p, miR-22-5p was associated with a higher metabolic risk profile, unfavourable macro- and microvascular health, lower physical activity (PA) as well as cardiorespiratory fitness (CRF) levels. Increased expression of miR-342-3p, miR-1-3p, miR-92b-5p, miR-454-3p, miR-190a-5p and miR-375-3p was associated with a lower metabolic risk profile, favourable macro- and microvascular health as well as higher PA and CRF. Of note, the first two principal components explained as much as 20% and 11% of the data variance. miRNAs and their potential target genes appear to mediate disease- and health-related physiological and pathophysiological adaptations that need to be validated and supported by further downstream analysis in future studies.Clinical Trial Registration: ClinicalTrials.gov: NCT02796976 (https://clinicaltrials.gov/ct2/show/NCT02796976).

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Hosen, D. R. « Circulating microRNA-122-5p is associated with a lack of improvement in left-ventricular function after TAVR and regulates viability of cardiomyocytes via extracellular vesicles ». European Heart Journal 43, Supplement_2 (1 octobre 2022). http://dx.doi.org/10.1093/eurheartj/ehac544.823.

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Abstract Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis (AVS). However, a specific role for circulating microRNAs (miRNAs) in the improvement of cardiac function for patients after TAVR has not yet been investigated. Herein, we profiled the differential expression of miRNAs in circulating extracellular vesicles (EV-miRNAs) in patients after TAVR and, in particular, the novel role of circulating miR-122-5p in cardiomyocytes. Circulating EV-associated miRNAs were investigated by using an unbiased Taqman-based human miR array. Several EV-miRNAs (miR-122-5p, miR-26a, miR-192, miR-483-5p, miR-720, miR-885-5p, and miR-1274) were significantly deregulated in aortic stenosis patients at day seven after TAVR in comparison to the pre-procedural levels in patients without LVEF-improvement. The higher levels of miR-122-5p were negatively correlated with LVEF improvement at both day seven (r=−0.264 and p=0.015) and at six months (r=−0.328 and p=0.0018) after TAVR. At the three-year follow-up, patients with a higher level of miR-122-5p displayed significantly increased cardiovascular mortality (p=0.03). By utilization of patient-derived samples and a murine aortic-stenosis model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Graded wire-injury-induced aortic-valve-stenotic mice demonstrated a higher level of miR-122-5p, which was related to cardiomyocytes dysfunction. Murine ex vivo experiments revealed that miR-122-5p is highly enriched in endothelial cells in comparison to cardiomyocytes. Gain- and loss-of-function experiments suggested that EV-mediated shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes and regulates the viability of cardiomyocytes. Mechanistically, miR pulldown, electrophoretic mobility shift assay, and RNA immunoprecipitation confirmed that miR-122-5p interacts with the RNA-binding protein, hnRNPU, in a sequence-specific manner to encapsulate miR-122-5p into large EVs. Upon shuttling into recipient cells, miR-122-5p reduces the expression of the anti-apoptotic gene BCL2, by binding to its 3' untranslated region to inhibit its translation, and thereby decreasing the viability of target cardiomyocytes. Increased levels of circulating pro-apoptotic EV-incorporated miR-122-5p are associated with reduced LVEF after TAVR. Extracellular vesicular shuttling of miR-122-5p regulates the viability and apoptosis of cardiomyocytes in a BCL2-dependent manner. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): German Research Foundation (DFG)German Society of Cardiology (DGK)

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