MicroRNA­137 has a suppressive role in liver cancer via targeting EZH2.

ABSTRACT

A variety of microRNAs (miRs) have been demonstrated to be associated with the development and malignant progression of human cancer; however, the regulatory mechanism of miR­137 underlying hepatocellular carcinoma (HCC) growth and metastasis still remains to be fully revealed. In the present study, reverse transcription­quantitative polymerase chain reaction and western blot were used to examine mRNA and protein expression. MTT assay, wound healing assay and Transwell assay were performed to determine cell proliferation, migration and invasion. Luciferase reporter assay was conducted to confirm the targeting relationship. miR­137 was significantly downregulated in HCC tissues compared to adjacent normal tissues. Low expression of miR­137 was significantly associated with lymph node metastasis, vein invasion, advanced clinical stage and poor prognosis in HCC. In addition, miR­137 was also downregulated in several liver cancer cell lines compared with normal liver epithelial cells. Overexpression of miR­137 led to a significant reduction in cell proliferation, migration and invasion of HepG2 cells. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) was further identified as a direct target gene of miR­137, and the protein expression of EZH2 was negatively regulated by miR­137 in HepG2 cells. Additionally, EZH2 was significantly upregulated in HCC tissues and liver cancer cell lines. Furthermore, overexpression of EZH2 significantly eliminated the inhibitory effects of miR­137 on the malignant phenotypes of HepG2 cells. Therefore, the findings suggest that miR­137 may have a suppressive role in HCC growth and metastasis via targeting EZH2.