Li Yong, Wu Dapeng, Wang Pei, Li Xiaohui, Shi Gongning
Department of Cardiothoracic Surgery, Huaihe Hospital of Henan University, Kaifeng 475000, China.
Dis Markers. 2017;2017:8317913. doi: 10.1155/2017/8317913. Epub 2017 Apr 9.
miR-195 is related to tumorigenesis and frequently inhibits cell proliferation and promotes apoptosis in various cancers, including esophageal carcinoma (EC). The mTOR/p70s6k signaling pathway, which is the major target pathway for HMGA2, regulates the survival and cell proliferation of many tumors and is commonly active in EC. The relationships of miR-195, HMGA2, and the mTOR/p70s6k signaling pathway in EC, however, remain unknown. In the present study, we found that the miR-195 level was significantly downregulated in EC tissues, while the mRNA expressions of HMGA2 were significantly upregulated. Dual-luciferase reporter assay demonstrated that HMGA2 is a target of miR-195. MTT assay and flow cytometry revealed that miR-195 overexpression inhibited cell proliferation and induced apoptosis by targeting HMGA2. We also found that HMGA2 restored the inhibitory effect of miR-195 on phosphorylation of mTOR and p70S6K. Furthermore, rapamycin, a specific inhibitor of the mTOR/p70S6K signaling pathway, decreased the levels of Ki-67 and Bcl-2/Bax ratio, inhibited cell proliferation, and promoted apoptosis in EC cells. In conclusion, upregulation of miR-195 significantly suppressed cell growth and induced apoptosis of EC cells via suppressing the mTOR/p70s6k signaling pathway by targeting HMGA2.
miR-195与肿瘤发生相关，并且在包括食管癌（EC）在内的多种癌症中常常抑制细胞增殖并促进细胞凋亡。mTOR/p70s6k信号通路是HMGA2的主要靶标通路，调节许多肿瘤的存活和细胞增殖，并且在食管癌中通常处于激活状态。然而，miR-195、HMGA2以及mTOR/p70s6k信号通路在食管癌中的关系仍不清楚。在本研究中，我们发现miR-195水平在食管癌组织中显著下调，而HMGA2的mRNA表达显著上调。双荧光素酶报告基因检测表明HMGA2是miR-195的一个靶标。MTT法和流式细胞术显示，miR-195过表达通过靶向HMGA2抑制细胞增殖并诱导细胞凋亡。我们还发现HMGA2恢复了miR-195对mTOR和p70S6K磷酸化的抑制作用。此外，雷帕霉素，一种mTOR/p70S6K信号通路的特异性抑制剂，降低了Ki-67水平和Bcl-2/Bax比值，抑制了食管癌细胞的增殖，并促进了其凋亡。总之，miR-195的上调通过靶向HMGA2抑制mTOR/p70s6k信号通路，显著抑制了食管癌细胞的生长并诱导其凋亡。
