Academic literature on the topic 'MiR-3192-5p'

Background Inflammation in epicardial adipose tissue (EAT) may contribute to coronary atherosclerosis. Myocardial bridge is a congenital anomaly in which the left anterior descending coronary artery takes a “tunneled” course under a bridge of myocardium: while atherosclerosis develops in the proximal left anterior descending coronary artery, the bridged portion is spared, highlighting the possibility that geographic separation from inflamed EAT is protective. We tested the hypothesis that inflammation in EAT was related to atherosclerosis by comparing EAT from proximal and bridge depots in individuals with myocardial bridge and varying degrees of atherosclerotic plaque. Methods and Results Maximal plaque burden was quantified by intravascular ultrasound, and inflammation was quantified by pericoronary EAT signal attenuation (pericoronary adipose tissue attenuation) from cardiac computed tomography scans. EAT overlying the proximal left anterior descending coronary artery and myocardial bridge was harvested for measurement of mRNA and microRNA (miRNA) using custom chips by Nanostring; inflammatory cytokines were measured in tissue culture supernatants. Pericoronary adipose tissue attenuation was increased, indicating inflammation, in proximal versus bridge EAT, in proportion to atherosclerotic plaque. Individuals with moderate‐high versus low plaque burden exhibited greater expression of inflammation and hypoxia genes, and lower expression of adipogenesis genes. Comparison of gene expression in proximal versus bridge depots revealed differences only in participants with moderate‐high plaque: inflammation was higher in proximal and adipogenesis lower in bridge EAT. Secreted inflammatory cytokines tended to be higher in proximal EAT. Hypoxia‐inducible factor 1a was highly associated with inflammatory gene expression. Seven miRNAs were differentially expressed by depot: 3192‐5P, 518D‐3P, and 532‐5P were upregulated in proximal EAT, whereas miR 630, 575, 16‐5P, and 320E were upregulated in bridge EAT. miR 630 correlated directly with plaque burden and inversely with adipogenesis genes. miR 3192‐5P, 518D‐3P, and 532‐5P correlated inversely with hypoxia/oxidative stress, peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PCG1a), adipogenesis, and angiogenesis genes. Conclusions Inflammation is specifically elevated in EAT overlying atherosclerotic plaque, suggesting that EAT inflammation is caused by atherogenic molecular signals, including hypoxia‐inducible factor 1a and/or miRNAs in an “inside‐to‐out” relationship. Adipogenesis was suppressed in the bridge EAT, but only in the presence of atherosclerotic plaque, supporting cross talk between the vasculature and EAT. miR 630 in EAT, expressed differentially according to burden of atherosclerotic plaque, and 3 other miRNAs appear to inhibit key genes related to adipogenesis, angiogenesis, hypoxia/oxidative stress, and thermogenesis in EAT, highlighting a role for miRNA in mediating cross talk between the coronary vasculature and EAT.

Circulating abundance of microRNAs (miRNA) are altered in youth with type 1 diabetes (T1D) and in response to a high fat meal, but whether T1D modifies the miRNA response to a meal is unknown. We identified miRNAs altered in youth with T1D compared to youth without T1D (control) after a high fat meal challenge, a novel approach to understanding how metabolic stress responses may be altered by T1D. Each group had 6 girls and 6 boys, similar in age (17.9±1.5 y), with normal BMI (65±22 and 43±15 percentile, respectively). Serum samples were collected at baseline and 150 min after meal consumption. The meal composition was 75 g carbohydrate, 50 g fat (31 g saturated fat), and 20 g protein. Participants with T1D administered insulin before the meal. Total RNA was extracted using the Qiagen miRNeasy Serum/Plasma Advanced Kit. The Nanostring nCounter Human v3 miRNA Panel was used for miRNA profiling. Abundance values were normalized for the number of reads across all samples. The data were fit to a linear model, and an empirical Baysean test was used to determine differences in circulating miRNAs between groups at baseline and after meal consumption. Significance was set as fold change greater than 0.5 with p<0.05. At baseline 17 miRNA species were lower in abundance in the youth with T1D while 16 were higher. In response to the meal, 3 miRNAs declined, and 4 miRNAs increased in the control group while 4 miRNAs declined, and 2 miRNAs increased in the T1D group. Compared to the control group, the T1D group had 19 miRNAs with smaller post-meal changes and 10 with larger changes. The changes in miR-573, miR-655-3p, and miR-769-5p were negatively correlated with glucose AUC and HbA1c, while the change in miR-3192-5p was positively correlated with glucose AUC and HbA1c. These finding show that T1D modifies responses in serum miRNA abundance following a high fat meal, and some of those differences are associated with glycemia. We postulate that the changes in miRNAs are mediated by glycemia, and future investigations will explore this mechanism. Disclosure W. Lee: None. B. Nelson: None. A.M. Teague: None. K.R. Short: None. J.B. Tryggestad: Other Relationship; Ascendis Pharma A/S. Funding Tracktenburg Endowment

Bien que la majorité des patientes atteintes d’un cancer de l’ovaire répondent initialement à une chimiothérapie à base de platine, la plupart d’entre-elles rechutent et développent une chimiorésistance, conduisant à une faible survie à 5 ans. Dans ce contexte, il est important de comprendre les mécanismes moléculaires impliqués dans la chimiorésistance pour développer de nouvelles approches thérapeutiques. Dans ce contexte, un criblage fonctionnel d’une banque de microARNs (miARNs) a permis d’identifier plusieurs miARNs qui sensibilisent deux lignées cancéreuses ovariennes chimiorésistantes (IGROV1-R10 et SKOV3) à l’action du cisplatine, dont le miR-3192-5p qui induit une mort cellulaire massive par apoptose et qui n’a jamais été précédemment étudié. L’action chimiosensiblisatrice de ce miARN a été ensuite validée sur une troisième lignée cancéreuse ovarienne chimiorésistance (OAW42-R). En utilisant une approche combinant bioinformatique et étude fonctionnelle, nous avons observé que le miR-3192-5p module l’expression de plusieurs protéines impliquées dans les mécanismes de réponses aux dommages et de réparation de l’ADN. Parmi ces cibles, nous avons démontré que la protéine ERCC1 est un déterminant de l’action chimiosensibilisatrice du miR-3192-5p dans les lignées cancéreuses ovariennes IGROV1-R10 et OAW42-R. Des résultats préliminaires montrent que la sensibilisation des cellules SKOV3 à l’action du cisplatine pourrait être reliée à l’inhibition de CHEK1, dont l’expression est diminuée en réponse au miR3192-5p. En résumé, ces travaux ont permis d’identifier de nouveaux miARNs impliqués dans la chimiorésistance des cancers de l’ovaire, et de caractériser plus précisément le rôle du miR-3192-5p et de certaines cibles impliquées dans son action chimiosensibilisatrice, ouvrant ainsi vers la proposition de nouvelles stratégies thérapeutiques pour améliorer la prise en charge de ces cancers
Although the majority of ovarian cancer patients initially respond to platinum-based chemotherapy, most of them relapse and develop chemoresistance, leading to poor 5-year survival. In this context, it is important to understand the molecular mechanisms involved in chemoresistance in order to develop new therapeutic approaches. In this context, a functional screening of a miRNA library identified several microRNAs (miRNAs) that sensitize two chemoresistant ovarian cancer lines (IGROV1-R10 and SKOV3) to the action of cisplatin, including miR-3192-5p, which induces massive cell death by apoptosis and has never been previously studied. The chemosensitizing effect of this miRNA was then validated on a third chemoresistant ovarian cancer line (OAW42-R). Using an approach combining bioinformatics and functional study, we observed that miR-3192-5p modulates the expression of several proteins involved in DNA damage response and repair mechanisms. Among these targets, we have demonstrated that the ERCC1 protein is a key determinant of the chemosensitizing effect of miR-3192-5p in the IGROV1-R10 and OAW42-R ovarian cancer lines. Preliminary results show that sensitization of SKOV3 cells to cisplatin action may be related to inhibition of CHEK1, whose expression is decreased in response to miR-3192-5p. In summary, this work has enabled us to identify new miRNAs involved in chemoresistance in ovarian cancers, and to characterize more precisely the role of miR-3192-5p and certain targets involved in its chemosensitizing action, opening the way to the proposal of new therapeutic strategies to improve the management of these cancers