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MiR-490-3p inhibits autophagy via targeting ATG7 in hepatocellular carcinoma

Yingliang Ou1, Jiafa He1, Yubin Liu1

  • 1Department of Hepatobiliary Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

IUBMB Life
|April 21, 2018
PubMed

Insights

MicroRNA-490-3p (miR-490-3p) suppresses hepatocellular carcinoma (HCC) cell proliferation and promotes apoptosis by inhibiting autophagy through targeting ATG7. Low miR-490-3p expression correlates with poor prognosis in HCC patients.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) is a major global health concern with limited treatment options.
  • MicroRNAs (miRNAs) play critical roles in cancer development and progression.
  • Dysregulation of autophagy is implicated in HCC pathogenesis.

Purpose of the Study:

  • To investigate the role of miR-490-3p in HCC.
  • To explore the correlation between miR-490-3p, HCC cell proliferation, apoptosis, and autophagy.
  • To identify the downstream target gene of miR-490-3p involved in HCC.

Main Methods:

  • Screening of miR-490-3p using gene microarray data.
  • Quantitative real-time PCR (qRT-PCR) for miR-490-3p expression analysis.
  • Transfection of miR-490-3p mimics into HepG2 cells.
  • Cell proliferation assays (colony formation, CCK-8).
  • Flow cytometry for cell cycle and apoptosis analysis.
  • Electron microscopy for autophagosome observation.
  • Western blot for autophagy-related protein analysis (LC-II, LC-I).
  • TCGA data analysis for prognosis.
  • Inhibition of autophagy using 3-MA and ATG7 knockdown.

Main Results:

  • miR-490-3p was significantly downregulated in HCC cell lines and tissues.
  • High miR-490-3p expression was associated with better patient prognosis.
  • miR-490-3p mimics transfection in HepG2 cells increased cell viability, enhanced proliferation, blocked cell cycle at G0/G1 phase, and increased apoptosis rate.
  • miR-490-3p transfection reduced autophagosome numbers and altered autophagy-related protein levels (decreased LC-II, increased LC-I, decreased LC-II/LC-I ratio).
  • Inhibition of autophagy (3-MA, ATG7 knockdown) promoted apoptosis and suppressed proliferation.
  • miR-490-3p targets ATG7, inhibiting autophagy and promoting apoptosis in HCC cells.

Conclusions:

  • miR-490-3p acts as a tumor suppressor in HCC.
  • miR-490-3p suppresses HCC cell proliferation and promotes apoptosis by inhibiting autophagy via targeting ATG7.
  • miR-490-3p represents a potential therapeutic target for HCC treatment.
Keywords:
ATG7MiR-490-3pautophagyhepatocellular carcinoma

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