MicroRNA-93 activates c-Met/PI3K/Akt pathway activity in hepatocellular carcinoma by directly inhibiting PTEN and

Katsuya Ohta1, Hiromitsu Hoshino1, Jinhua Wang1

  • 1Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.

Oncotarget
|January 31, 2015
PubMed

Insights

MicroRNA-93 (miR-93) promotes hepatocellular carcinoma (HCC) progression by enhancing cell proliferation and invasion. Targeting miR-93 may improve treatment outcomes for HCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Hepatocellular carcinoma (HCC) is a major global health concern.
  • The role of microRNAs (miRNAs) in HCC pathogenesis is increasingly recognized.
  • Identifying novel molecular targets is crucial for improving HCC treatment.

Purpose of the Study:

  • To investigate the role of miR-93 in hepatocellular carcinoma.
  • To elucidate the molecular mechanisms underlying miR-93's function in HCC.
  • To assess the prognostic significance of miR-93 in HCC patients.

Main Methods:

  • MicroRNA expression profiling in HCC cell lines.
  • Quantitative real-time PCR (qRT-PCR) for miR-93 expression analysis in HCC tumors.
  • In vitro assays for cell proliferation, migration, invasion, and apoptosis.
  • Western blotting and immunohistochemistry (IHC) for protein expression analysis.
  • Luciferase reporter assays to confirm direct binding of miR-93 to target genes.

Main Results:

  • miR-93 was identified as a novel miRNA associated with HCC.
  • Elevated miR-93 expression correlated significantly with poor prognosis in advanced HCC.
  • miR-93 overexpression promoted HCC cell proliferation, migration, and invasion, while inhibiting apoptosis.
  • miR-93 directly targeted and inhibited the tumor suppressor genes PTEN and CDKN1A.
  • Inhibition of PTEN and CDKN1A by miR-93 led to enhanced activation of the c-Met/PI3K/Akt pathway.
  • Knockdown of c-Met reduced miR-93 expression and inhibited the c-Met/PI3K/Akt pathway.
  • miR-93 sensitized HCC cells to sorafenib and tivantinib treatments.

Conclusions:

  • miR-93 acts as an oncogenic miRNA in HCC.
  • miR-93 promotes HCC progression by activating the c-Met/PI3K/Akt pathway and inhibiting PTEN and CDKN1A.
  • miR-93 may serve as a potential therapeutic target and prognostic biomarker for HCC.

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