Zhang Jing-Shu, Zhao Yue, Lv Yuan, Liu Pei-Yan, Ruan Jun-Xia, Sun Yue-Ling, Gong Tian-Xing, Wan Nan, Qiu Guang-Rong
Department of Medical Genetics, College of Basic Medical Science, China Medical University, Shenyang, PR China; Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, PR China.
Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, PR China.
Gene. 2017 Aug 30;626:426-432. doi: 10.1016/j.gene.2017.05.062. Epub 2017 Jun 2.
MicroRNAs (miRNAs) are a class of endogenous, non-coding small RNAs that regulate the expression of target genes. Previous studies have suggested that miRNAs are key regulators in cardiovascular systems. This study investigated the role of miR-873 in H9C2 cardiomyocytes by targeting glioma-associated oncogene 1 (GLI1). miR-873 was significantly up-regulated in serum samples from congenital heart disease (CHD) patients compared with those from normal individuals. Furthermore, miR-873 over-expression suppressed H9C2 proliferation and induced cell cycle arrest. Bioinformatic algorithms revealed a predicted target site for miR-873 in the 3'-untranslated region (3'UTR) of GLI1, which was verified using a dual-luciferase reporter assay. qPCR and western blot analysis also showed that miR-873 negatively regulated GLI1 mRNA and protein expression in H9C2 cells. Conversely, GLI1 over-expression partially reversed the growth-inhibitory effect of miR-873. To summarize, our data suggest that miR-873 is a novel miRNA that regulates H9C2 cell proliferation via targeting GLI1, and miR-873 may serve as a new potential biomarker diagnosis in CHD in the future.
微小RNA（miRNA）是一类内源性非编码小RNA，可调节靶基因的表达。先前的研究表明，miRNA是心血管系统中的关键调节因子。本研究通过靶向胶质瘤相关癌基因1（GLI1）来探究miR-873在H9C2心肌细胞中的作用。与正常个体相比，先天性心脏病（CHD）患者血清样本中的miR-873显著上调。此外，miR-873过表达抑制H9C2增殖并诱导细胞周期停滞。生物信息学算法揭示了GLI1的3'非翻译区（3'UTR）中miR-873的预测靶位点，这通过双荧光素酶报告基因检测得到验证。qPCR和蛋白质印迹分析还表明，miR-873在H9C2细胞中负调节GLI1的mRNA和蛋白质表达。相反，GLI1过表达部分逆转了miR-873的生长抑制作用。总之，我们的数据表明，miR-873是一种通过靶向GLI1调节H9C2细胞增殖的新型miRNA，并且miR-873未来可能作为CHD的一种新的潜在生物标志物用于诊断。
