Overexpression of miR-607 inhibits hepatocellular carcinoma cell growth and metastasis by down-regulating TRPC5.
10.12122/j.issn.1673-4254.2022.11.01
- Author:
Chao LI
1
;
Shuang Jiang CHEN
2
;
Ye Zhen JIANG
3
Author Information
1. Department of Hepatopancreatobiliary Surgery, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, China.
2. Department of General Surgery, Ankang People's Hospital, Ankang 725000, China.
3. Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
- Publication Type:Journal Article
- Keywords:
Akt signal pathway;
TRPC5;
hepatocellular carcinoma;
metastasis;
miR-607
- MeSH:
Humans;
Carcinoma, Hepatocellular/genetics*;
Liver Neoplasms/genetics*;
Cell Line;
Cell Proliferation;
3' Untranslated Regions;
MicroRNAs/genetics*;
TRPC Cation Channels/genetics*
- From:
Journal of Southern Medical University
2022;42(11):1587-1593
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the clinical implications of abnormal expression of miR-607 in hepatocellular carcinoma (HCC) and its influence on HCC cell proliferation and migration.
METHODS:The expression of miR-607 in 45 pairs of HCC and adjacent tissues were detected with real-time PCR, and the correlation between miR-607 expression and clinicopathological features of the patients was analyzed. The effects of transfection with miR-607 mimics on proliferation, apoptosis, migration and invasion of two HCC cell lines (Huh-7 and HCCLM3) were evaluated using CCK-8 assay, flow cytometry, wound-healing assay and Transwell assay. A dual-luciferase reporter system was used to detect the direct binding between miR-607 and 3'-UTR of TRPC5 mRNA. Western blotting was used to measure the expressions of TRPC5, CCND1, MMP2 and phosphorylated Akt in the HCC cells.
RESULTS:The expression of miR-607 was significantly decreased in HCC tissues (P=0.029) and HCC cell lines (P < 0.05). In HCC patients, a low expression of miR-607 was associated with a larger tumor size (>5 cm, P=0.031), vascular invasion (P=0.027) and advanced TNM stages (Ⅲ + Ⅳ, P=0.015). In the two HCC cell line, overexpression of miR-607 significantly inhibited cell proliferation, migration, and invasion and enhanced cell apoptosis (P < 0.05). The results of dualluciferase reporter assay confirmed that TRPC5 was a direct target of miR- 607 in HCC cells. Overexpression of miR-607 significantly inhibited the expressions of TRPC5, CCND1, and MMP2 and suppressed Akt phosphorylation in HCC cells (P < 0.05).
CONCLUSION:A low expression of miR-607 in HCC is associated with poor clinicopathological phenotypes of HCC. Overexpression of miR-607 inhibits HCC growth and metastasis possibly by down- regulating TRPC5, which causes Akt signaling inactivation.
