Circulating miRNA-1-3p as Biomarker of Accelerated Sarcopenia in Patients Diagnosed with Chronic Heart Failure

ABSTRACT Background: While sarcopenia is an important clinical finding in individuals diagnosed with chronic heart failure (CHF), efforts to identify a reliable biomarker capable of predicting the overall muscular and functional decline in CHF patients have been unsuccessful to date. Objectives: The objectives of this study were to study the diagnostic utility of MicroRNA (miRNA)-1-3p as a predictor of sarcopenia status in individuals diagnosed with CHF. Methods: In total, 80 individuals with heart failure exhibiting a left ventricular ejection fraction < 50% were enrolled in this study. All patients were analyzed to assess miR-1-3p expression levels, with body composition being evaluated through dual-energy X-ray absorptiometry and sarcopenia being defined based on the sum of appendicular lean muscle mass (ALM) divided by height in meters squared and handgrip strength (HGS). In addition, the activation of the Akt/mTOR signaling pathway was evaluated in these individuals. Results: In total, 40 of the enrolled patients (50%) exhibited sarcopenia. Sarcopenic patients presented with increased miR-1-3p expression levels as compared to non-sarcopenic individuals (1.69 ± 0.132 vs. 1.22 ± 0.106; p < 0.05). With respect to sarcopenic indices, appendicular skeletal mass index was most strongly correlated with miR-1-3p expression, which was also strongly correlated with HGS. High levels of Akt/mTOR signaling pathway components were expressed in sarcopenic individuals, highlighting a significant relationship between miR-1-3p activity and signaling through this pathway. Moreover, miR-1-3p was identified as a specific marker for sarcopenia in individuals with CHF. Conclusion: These results suggest that circulating miR-1-3p levels are related to Akt/mTOR pathway activation and can offer valuable insight into the overall physical capacity and muscular integrity of CHF patients as a predictor of sarcopenia.

Screening and validation of markers related to diagnosis and prognosis assessment of gastric cancer based on miRNA-mRNA network and their potential molecular mechanisms / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：通过生物信息学方法探索并实验验证胃癌相关标志物miR-1-3p对胃癌细胞增殖的作用及其分子机制。方法：收集TCGA数据库中胃癌（n=375）及癌旁组织（n=45）的转录组数据，构建胃癌特异性mRNA-miRNA网络，筛选潜在的miRNA类标志物，利用TargetScan预测标志物的下游靶基因且分析它们的功能。选取人正常胃上皮细胞GES-1及胃癌细胞AGS、MKN45、NCI-N87，用qPCR法检测细胞中miR-1-3p和心肌蛋白（MYOCD）的表达，用lipofectamine 2000将miR-1-3p模拟物转染至胃癌细胞中，CCK-8法测定轨染后细胞的增殖能力，WB法测定MYOCD的表达量，双荧光素酶报告基因实验验证miR-1-3p与MYOCD之间的靶向结合关系。结果：通过数据库数据分析得到差异表达的259个miRNA和7 545个mRNA，构建胃癌特异性mRNA-miRNA调节网络，分析网络中脆弱结构后确定miR-1-3p为潜在的胃癌标志物，ROC曲线和Kaplan-Meier分析显示其对胃癌的诊断和预后评估有重要意义。细胞实验显示miR-1-3p在胃癌细胞中呈低表达（P<0.05），过表达miR-1-3p可抑制胃癌细胞AGS和MKN-45的增殖能力（P<0.05或P<0.01），且可抑制MYOCD的表达（P<0.01）。TargetScan数据库预测到MYOCD的3'UTR区域中有两个与miR-1-3p结合的位点，双荧光素酶报告基因实验证实miR-1-3p与MYOCD靶向结合且负调控MYOCD的表达（P<0.01）。结论: miR-1-3p可能是胃癌诊断和预后相关潜在的标志物，且miR-1-3p可能是通过靶向MYOCD来影响胃癌细胞的增殖。