Pan Wen, Zhang Yanan, Zeng Chun, Xu Fen, Yan Jinhua, Weng Jianping
Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
Department of Emergency, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
Exp Ther Med. 2018 Sep;16(3):2717-2724. doi: 10.3892/etm.2018.6453. Epub 2018 Jul 17.
MicroRNAs (miRs) post-translationally regulate gene expression by specifically binding to the mRNA of their target genes. The aim of the present study was to determine the effect of miR-192 on pancreatic β-cell development. The serum levels of miR-192 in type 1 diabetes mellitus (T1DM) and streptozotocin-induced rats were determined, and were revealed to be elevated compared with those in healthy patients and normal rats, respectively. Western blot and reverse transcription-quantitative polymerase chain reaction analysis indicated that miR-192 suppressed the expression of glucagon-like peptide-1 (GLP-1), a potent insulin secretagogue. Ectopic expression of miR-192 inhibited cell proliferation and promoted apoptosis of NIT-1 cells, while miR-192 inhibitor had the opposite effect. Collectively, the present results revealed that miR-192 was elevated in T1DM, and is implicated in pancreatic β-cell development through regulation of cell proliferation and apoptosis, thereby suppressing insulin secretion. Furthermore, miR-192 suppressed GLP-1 expression, thereby further promoting T1DM. The present study suggested that miR-192 is a novel molecular target for the management or prevention of T1DM.
微小RNA（miR）通过特异性结合其靶基因的mRNA在翻译后调节基因表达。本研究的目的是确定miR-192对胰腺β细胞发育的影响。测定了1型糖尿病（T1DM）患者和链脲佐菌素诱导的大鼠血清中miR-192的水平，结果显示分别高于健康患者和正常大鼠。蛋白质印迹法和逆转录-定量聚合酶链反应分析表明，miR-192抑制了胰高血糖素样肽-1（GLP-1）的表达，GLP-1是一种有效的胰岛素促分泌剂。miR-192的异位表达抑制了NIT-1细胞的增殖并促进了其凋亡，而miR-192抑制剂则具有相反的作用。总体而言，目前的结果表明，miR-192在T1DM中升高，并通过调节细胞增殖和凋亡参与胰腺β细胞发育，从而抑制胰岛素分泌。此外，miR-192抑制GLP-1表达，从而进一步促进T1DM。本研究表明，miR-192是管理或预防T1DM的一个新的分子靶点。
