Epigenetic modification of MiR-429 promotes liver tumour-initiating cell properties by targeting Rb binding protein 4

  • 0International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China.

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Summary

This summary is machine-generated.

Epigenetic modification of miR-429 regulates liver tumor-initiating cells (T-ICs) by targeting the RBBP4/E2F1/OCT4 axis. This miRNA offers a novel strategy for hepatocellular carcinoma (HCC) prevention and treatment.

Area Of Science

  • Hepatology and Cancer Biology
  • Epigenetics and Molecular Oncology

Background

  • Liver tumour-initiating cells (T-ICs) are crucial for hepatocellular carcinoma (HCC) development.
  • The regulatory mechanisms governing liver T-IC function remain incompletely understood.

Purpose Of The Study

  • To elucidate the role of miR-429 in regulating liver T-ICs.
  • To identify the molecular pathways involved in miR-429-mediated T-IC regulation.
  • To explore the therapeutic potential of targeting miR-429 in HCC.

Main Methods

  • Prognostic analysis using tissue microarrays from 242 HCC samples.
  • Isolation of EpCAM-positive T-ICs via magnetically activated cell sorting.
  • Gene expression profiling, co-immunoprecipitation, and quantitative methylation analysis.
  • In vitro and in vivo validation of the miR-429 regulatory axis.

Main Results

  • miR-429 is upregulated in HCC tissues and T-ICs, correlating with prognosis.
  • miR-429 enrichment in EpCAM+ T-ICs promotes self-renewal, proliferation, chemoresistance, and tumorigenicity.
  • A novel axis involving miR-429, RBBP4, E2F1, and OCT4 regulates liver T-ICs.
  • Abnormal hypomethylation upstream of the miR-200b/200a/429 cluster regulates miR-429 expression in T-ICs and early HCC.

Conclusions

  • Epigenetic modulation of miR-429 impacts liver T-ICs via the RBBP4/E2F1/OCT4 pathway.
  • Targeting miR-429 presents a potential strategy for HCC prevention and treatment by inactivating T-ICs.

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