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Am J Transl Res. 2017 Dec 15;9(12):5576-5584. eCollection 2017.

MicroRNA-423 enhances the invasiveness of hepatocellular carcinoma via regulation of BRMS1.

Author information

1
Department of Hepatobiliary Surgery, Linyi People's HospitalLinyi 276003, China.
2
Operating Department, Linyi People's HospitalLinyi 276003, China.
3
Nursing Department, Linyi People's HospitalLinyi 276003, China.
4
Department of Gastroenterology, Linyi People's HospitalLinyi 276003, China.

Abstract

Tumor metastasis portrayed the most serious challenges of cancer as it is the major cause of mortality in patients with solid tumors, including hepatocellular carcinoma (HCC). In this regard, anti-metastatic genes have a great potential for metastasis inhibition. Recent evidence pointed to a role of Breast cancer metastasis suppressor 1 (BRMS1) in suppression of metastasis of several types of cancers, whereas the regulation of BRMS1 in HCC remains unknown. Here, we used bioinformatics analyses to predict BRMS1-targeting microRNAs (miRNAs), and evaluated the functional binding of miRNAs to BRMS1 mRNA using a dual luciferase reporter assay. Among all BRMS1-targeting miRNAs, we only detected significant expression of miR-626, miR-1289 and miR-423 in HCC specimens. Specifically, we found that only miR-423 significantly inhibited protein translation of BRMS1 via specific binding to 3'-UTR of the BRMS1 mRNA. Moreover, we detected significantly lower levels of BRMS1 and significantly higher levels of miR-423 in the HCC specimens, relative to paired adjacent non-tumor liver tissue. Furthermore, BRMS1 and miR-423 levels were correlated inversely. Overexpression of miR-423 significantly decreased BRMS1 levels and promoted HCC cell invasion, while depletion of miR-423 significantly increased BRMS1 levels and inhibited HCC cell invasion. This study sheds light on miR-423 as a crucial factor that enhances HCC cell invasiveness, and suggests miR-423 as a promising therapeutic target for HCC treatment.

KEYWORDS:

Hepatocellular carcinoma (HCC); breast cancer metastasis suppressor 1 (BRMS1); miR-423

PMID:
29312509
PMCID:
PMC5752907

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