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Mutant ACTB mRNA 3'-UTR promotes hepatocellular carcinoma development by regulating miR-1 and miR-29a

Yong Li1, Hongbin Ma1, Changying Shi2

  • 1Department of Radiation Oncology, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.

Cellular Signalling
|December 18, 2019
PubMed

Insights

Mutant ACTB mRNA 3'-UTR promotes hepatocellular carcinoma (HCC) development by interacting with miR-1 and miR-29a. This interaction up-regulates MET and MCL1, driving cancer cell migration and invasion.

Area of Science:

  • Molecular Biology
  • Oncology
  • Hepatocellular Carcinoma Research

Background:

  • Actin beta (ACTB) is implicated in various cancers, but its specific role in hepatocellular carcinoma (HCC) remains unclear.
  • Limited research exists on the function and mechanisms of ACTB, particularly its mutant mRNA 3 -untranslated region (UTR), in HCC development.

Purpose of the Study:

  • To investigate the expression and biological functions of mutant ACTB mRNA 3 -UTR in hepatocellular carcinoma (HCC).
  • To elucidate the molecular mechanisms by which mutant ACTB mRNA 3 -UTR influences HCC progression.

Main Methods:

  • Transcriptome sequencing and quantitative reverse transcription PCR (qRT-PCR) to analyze ACTB expression.
  • Luciferase reporter assays to assess interactions between ACTB mRNA 3 -UTR and microRNAs (miRNAs).
  • In vitro and in vivo assays to evaluate the impact of mutant ACTB mRNA 3 -UTR on HCC cell behavior.

Main Results:

  • Mutant ACTB mRNA 3 -UTR exhibited high expression in HCC tumor tissues.
  • ACTB mRNA 3 -UTR mutations facilitated interactions with miR-1 and miR-29a, leading to their degradation via AGO2.
  • Mutant ACTB mRNA 3 -UTR promoted HCC cell migration and invasion by up-regulating MET (miR-1 target) and MCL1 (miR-29a target).

Conclusions:

  • The 3 -UTR of ACTB plays a critical role in the pathogenesis of hepatocellular carcinoma (HCC).
  • Mutant ACTB mRNA 3 -UTR contributes to HCC development through a mechanism involving miR-1, miR-29a, MET, and MCL1.
Keywords:
Hepatocellular carcinomaMutant ACTB mRNA 3′-UTRmiR-1miR-29a

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