Mei Li-Li, Wang Wen-Jun, Qiu Yun-Tan, Xie Xiu-Feng, Bai Jie, Shi Zhi-Zhou
Medical School, Kunming University of Science and Technology, Kunming 650500, China.
State Key Laboratory of Molecular Oncology, Cancer Hospital, CAMS, Beijing 100021, China.
Int J Mol Sci. 2017 Aug 23;18(9):1833. doi: 10.3390/ijms18091833.
MicroRNAs (miRNAs) play important roles in the progression of human cancer. Although previous reports have shown that miR-145-5p is down-regulated in esophageal squamous cell carcinoma (ESCC), the roles and mechanisms of down-regulation of miR-145-5p in ESCC are still largely unknown. Using microRNA microarray and Gene Expression Omnibus (GEO) datasets, we confirmed that miR-145-5p was down-regulated in ESCC tissues. In vitro assays revealed that ectopic miR-145-5p expression repressed cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT). miR-145-5p also reduced the expressions of cell cycle genes including cyclin A2 (), cyclin D1 () and cyclin E1 (), the EMT-associated transcription factor Slug, and matrix metalloproteinases (MMPs) including , and . Furthermore, miR-145-5p mimics reduced candidate target gene specificity protein 1 () and nuclear factor κ B () () both in mRNA and protein levels. Knockdown of phenocopied the effects of miR-145-5p overexpression on cell cycle regulators, EMT and the expression of (). Importantly, inhibition of the signaling pathway or knockdown of () phenocopied the effects of miR-145-5p on the migration, invasion and EMT of ESCC cells. In conclusion, our results suggested that miR-145-5p plays tumor-suppressive roles by inhibiting esophageal cancer cell migration, invasion and EMT through regulating the signaling pathway.
微小RNA（miRNA）在人类癌症进展中发挥着重要作用。尽管先前的报道表明miR-145-5p在食管鳞状细胞癌（ESCC）中表达下调，但其在ESCC中下调的作用和机制仍 largely unknown。利用微小RNA微阵列和基因表达综合数据库（GEO）数据集，我们证实miR-145-5p在ESCC组织中表达下调。体外实验表明，异位表达miR-145-5p可抑制细胞增殖、迁移、侵袭以及上皮-间质转化（EMT）。miR-145-5p还降低了包括细胞周期蛋白A2（）、细胞周期蛋白D1（）和细胞周期蛋白E1（）在内的细胞周期基因的表达，EMT相关转录因子Slug以及包括 、 和 在内的基质金属蛋白酶（MMP）的表达。此外，miR-145-5p模拟物在mRNA和蛋白质水平上均降低了候选靶基因特异性蛋白1（）和核因子κB（）（）的表达。敲低 可模拟miR-145-5p过表达对细胞周期调节因子、EMT以及 （）表达的影响。重要的是，抑制 信号通路或敲低 （）可模拟miR-145-5p对ESCC细胞迁移、侵袭和EMT的影响。总之，我们的结果表明，miR-145-5p通过调节 信号通路抑制食管癌细胞的迁移、侵袭和EMT，从而发挥肿瘤抑制作用。
