MicroRNA-449a suppresses hepatocellular carcinoma cell growth via G1 phase arrest and the HGF/MET c-Met pathway.

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MicroRNA-449a suppresses hepatocellular carcinoma cell growth via G1 phase arrest and the HGF/MET c-Met pathway.

Hepatobiliary Pancreat Dis Int. 2018 Aug;17(4):336-344

Authors: Cheng J, Wu LM, Deng XS, Wu J, Lv Z, Zhao HF, Yang Z, Ni Y

Abstract
BACKGROUND: Accumulating evidence demonstrates that microRNAs (miRNAs) play essential roles in tumorigenesis and cancer progression of hepatocellular carcinoma (HCC). Average targets of a miRNA were more than 100. And one miRNA may act in tumor via regulating several targets. The present study aimed to explore more potential targets of miR-449a by proteomics technology and further uncover the role of miR-449a in HCC tumorigenesis.
METHODS: Technologies such as iTRAQ-based quantitative proteomic were used to investigate the effect of miR-449a on HCC. The expression of c-Met and miR-449a was detected by qRT-PCR in HCC samples. Gain- and loss-of-function experiments were performed to identify the function and potential target of miR-449a in HCC cells.
RESULTS: In HCC, miR-449a was significantly downregulated, while c-Met was upregulated concurrently. Quantitative proteomics and luciferase reporter assay identified c-Met as a direct target of miR-449a. Moreover, miR-449a inhibited HCC growth not only by targeting CDK6 but also by suppressing c-Met/Ras/Raf/ERK signaling pathway. Furthermore, the inhibition of c-Met expression with a specific siRNA significantly inhibited cells growth and deregulated the ERK pathway in HCC.
CONCLUSION: The tumor suppressor miR-449a suppresses HCC tumorigenesis by repressing the c-Met/ERK pathway.

PMID: 30108016 [PubMed - indexed for MEDLINE]

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