Wu Xiaoyu, Deng Liang, Tang Decai, Ying Gang, Yao Xuequan, Liu Fukun, Liang Gui
Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, China.
Department of Hepatobiliary Surgery, the Eastern Hospital of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, China., Sun Yat-sen University, Guangzhou, 510700, People's Republic of China.
Tumour Biol. 2016 May;37(5):6813-21. doi: 10.1007/s13277-015-4506-8. Epub 2015 Dec 10.
It has been reported that miR-615-5p was upregulated in hepatocellular carcinoma (HCC) preventing both growth and migration. However, the underlying mechanism by which miR-615-5p played a role in HCC remains unknown. Here, in our present study, to investigate the mechanism of miR-615-5p, bioinformatic prediction and luciferase reporter assay were employed to ascertain the downstream target of miR-615-5p finding that the serine hydromethyltransferase 2 (SHMT2) was the direct downstream target. Knockdown or overexpression of miR-615-5p can lead to increasing or decreasing expression of SHMT2 in HCC cells. Besides, knockdown or overexpression of SHMT2 can suppress or promote both proliferation and migration of HCC cells, indicating that miR-615-5p can directly and negatively regulate the SHMT2 in HCC cells. In addition, to understand the clinicopathological significance of SHMT2 expression in HCC, immunohistochemistry was performed. It was found that SHMT2 expression was significantly associated with poor prognosis and TNM stage. Together, our results for the first time showed that miR-615-5p prevents proliferation and migration through negatively regulating SHMT2 in HCC.
据报道,miR-615-5p在肝细胞癌(HCC)中表达上调,可抑制细胞生长和迁移。然而,miR-615-5p在HCC中发挥作用的潜在机制仍不清楚。在本研究中,为了探究miR-615-5p的作用机制,我们采用生物信息学预测和荧光素酶报告基因检测来确定miR-615-5p的下游靶点,发现丝氨酸羟甲基转移酶2(SHMT2)是其直接下游靶点。敲低或过表达miR-615-5p可导致HCC细胞中SHMT2表达的降低或增加。此外,敲低或过表达SHMT2可抑制或促进HCC细胞的增殖和迁移,这表明miR-615-5p可直接负向调节HCC细胞中的SHMT2。另外,为了了解SHMT2在HCC中表达的临床病理意义,我们进行了免疫组织化学检测。结果发现,SHMT2的表达与预后不良及TNM分期显著相关。总之,我们的研究结果首次表明,miR-615-5p通过负向调节HCC中的SHMT2来抑制细胞增殖和迁移。