Epigenetic modification of MiR-429 promotes liver tumour-initiating cell properties by targeting Rb binding protein 4
- Liang Li 1, Jing Tang 1, Baohua Zhang 2, Wen Yang 1, Miyang LiuGao 1, Ruoyu Wang 3, Yexiong Tan 1, Jianling Fan 4, Yanxin Chang 3, Jing Fu 1, Feng Jiang 3, Caiyang Chen 3, Yingcheng Yang 1, Jin Gu 5, Dingming Wu 5, Linna Guo 1, Dan Cao 1, Hengyu Li 3, Guangwen Cao 6, Mengchao Wu 2, Michael Q Zhang 5, Lei Chen 1, Hongyang Wang 7
- Liang Li 1, Jing Tang 1, Baohua Zhang 2
- 1International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China.
- 2Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
- 3International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China.
- 4International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China Changzheng Hospital, Second Military Medical University, Shanghai, China.
- 5Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, Beijing, China.
- 6Department of Epidemiology, Second Military Medical University, Shanghai, China.
- 7International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China National Laboratory for Oncogenes and Related Genes, Cancer Institute, Ruijing Hospital, Shanghai Jiao Tong University, Shanghai, China.
- 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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View abstract on PubMed
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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