MicroRNA-137 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 miR-137 underlying hepatocellular carcinoma (HCC) growth and metastasis still remains to be fully revealed. In the present study, reverse transcription-quantitative 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. miR-137 was significantly downregulated in HCC tissues compared to adjacent normal tissues. Low expression of miR-137 was significantly associated with lymph node metastasis, vein invasion, advanced clinical stage and poor prognosis in HCC. In addition, miR-137 was also downregulated in several liver cancer cell lines compared with normal liver epithelial cells. Overexpression of miR-137 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 miR-137, and the protein expression of EZH2 was negatively regulated by miR-137 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 miR-137 on the malignant phenotypes of HepG2 cells. Therefore, the findings suggest that miR-137 may have a suppressive role in HCC growth and metastasis via targeting EZH2.

<p>Silencing Of hsa_circ_0008450 Represses Hepatocellular Carcinoma Progression Through Regulation Of microRNA-214-3p/EZH2 Axis</p>

“…36 Cui et al have found that miR-137 inhibited HCC growth and metastasis by suppressing the expression of EZH2. 38 Here, bioinformatics analysis and dual luciferase reporter assay showed that EZH2 was a target gene of miR-214-3p, and we identified the functional role of miR214-3p/EZH2 axis in HCC cells.…”

The Role of MicroRNAs in Hepatocellular Carcinoma

“…High expression of miR-92a 25 , miR-221 40 , miR-487a 45 and miR-1468 51 might indicate poor prognosis in HCC. Low expression of miR-33a 63 , miR-122 72 , miR-137 76 , miR-194 90 and miR-940 142 in HCC patients were observed to have unfavorable prognosis. High levels of miR-7/21/107 and low expression of maspin implied poor survival of HBV-related HCC 56 .…”

“…Low expression of miR-296 in HCC patients might have large tumor size and advanced TNM stage 108 . Low expression of miR‑137 was significantly closely related with lymph node metastasis, vein invasion and advanced clinical stage in HCC 76 .…”

“…Another report found that miR-122 could downregulate the expression of oncogenic distal-less 4 (DLX4), knockdown the expression of this oncogene would inhibit HCC cells proliferation 73 . Overexpression of miR-137 was reported to reduce HepG2 cells proliferation by targeting EZH2 76 . MiR-217 overexpression was revealed to inhibit cells apoptosis by targeting metadherin (MTDH) in HCC 105 .…”

“…Overexpression of miR-187-3p 89 , miR-199b-5p 98 and miR-1301 146 in HCC were also reported to inhibit EMT and metastasis. Besides, some miRNAs overexpression could repress invasion, migration and metastasis in HCC, for instance, miR-137 76 , miR-146a 85 , miR-186 88 , miR-199 94 , miR-365 116 , miR-370 118 , miR-520f 128 , miR-634 134 , miR-1207-5p 143 , and so on.…”