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Distinct anti-oncogenic effect of various microRNAs in different mouse models of liver cancer

Junyan Tao1,2, Junfang Ji3,4, Xiaolei Li2,5

  • 1School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, P.R. China.

Oncotarget
|March 13, 2015
PubMed

Insights

MicroRNAs (miRNAs) play a role in liver cancer. This study found that miR-101 acts as a tumor suppressor in hepatocellular carcinoma models, regardless of the specific oncogene driving the cancer, suggesting its therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA (miRNA) deregulation is common in human hepatocellular carcinoma (HCC).
  • The in vivo role of miRNAs during hepatocarcinogenesis is not well understood.
  • Distinct miRNA expression profiles are observed in mouse liver tumors induced by different oncogenes.

Purpose of the Study:

  • To investigate the in vivo relevance of specific downregulated miRNAs in hepatocarcinogenesis.
  • To determine the tumor suppressor activity of selected miRNAs in mouse models of liver cancer.
  • To assess the impact of oncogene-specific miRNA modulation on liver tumor development.

Main Methods:

  • Induction of liver tumors in mice using c-Myc or AKT/Ras overexpression.
  • Hydrodynamic transfection to overexpress selected miRNAs alongside oncogenes.
  • Evaluation of tumor suppressor activity of eight downregulated miRNAs (miR-101, miR-107, miR-122, miR-29, miR-365, miR-375, miR-378, miR-802).

Main Results:

  • Tumor suppressor activity of miRNAs varied significantly between c-Myc and AKT/Ras driven tumors.
  • miR-378 showed no tumor suppressor activity; miR-107, miR-122, miR-29, miR-365, and miR-802 had weak to moderate activity.
  • miR-375 demonstrated differential activity, inhibiting AKT/Ras driven tumors more effectively than c-Myc driven tumors.
  • miR-101 significantly suppressed tumor development in both c-Myc and AKT/Ras models.

Conclusions:

  • Different oncogenes induce distinct miRNA expression patterns that differentially impact hepatocarcinogenesis.
  • miR-101 exhibits potent tumor suppressor activity in liver cancer models, irrespective of the driving oncogene.
  • miR-101 represents a promising therapeutic target for human hepatocellular carcinoma.
Keywords:
AKTHCCRasc-Mycmouse liver cancer

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