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

Jun Cheng1, Li-Ming Wu2, Xue-Song Deng1

  • 1Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China.

Hepatobiliary & Pancreatic Diseases International : HBPD INT
|August 16, 2018
PubMed
Abstract

Insights

MicroRNA-449a (miR-449a) acts as a tumor suppressor in hepatocellular carcinoma (HCC). It inhibits HCC growth by targeting c-Met and repressing the c-Met/ERK pathway, offering potential therapeutic strategies for liver cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are crucial in hepatocellular carcinoma (HCC) development and progression.
  • HCC involves complex regulatory networks with single miRNAs targeting multiple genes.
  • Identifying novel miRNA targets is key to understanding HCC tumorigenesis.

Purpose of the Study:

  • To investigate potential targets of miR-449a in HCC using proteomics.
  • To elucidate the role of miR-449a in HCC tumorigenesis and its regulatory mechanisms.

Main Methods:

  • iTRAQ-based quantitative proteomics to analyze protein expression changes.
  • Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for gene expression analysis.
  • Gain- and loss-of-function experiments in HCC cells to determine miR-449a function and targets.

Main Results:

  • miR-449a was downregulated, and c-Met was concurrently upregulated in HCC.
  • Proteomics and luciferase assays confirmed c-Met as a direct miR-449a target.
  • miR-449a suppressed HCC growth by targeting CDK6 and inhibiting the c-Met/Ras/Raf/ERK pathway.

Conclusions:

  • miR-449a functions as a tumor suppressor in HCC.
  • Repression of the c-Met/ERK pathway by miR-449a inhibits HCC progression.
Keywords:
Hepatocellular carcinomaProteomicsTumorigenesisc-MetmiR-449a

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