title: MBD3 inhibits formation of liver cancer stem cells.
abstract: Liver cancer cells can be reprogrammed into induced cancer stem cells (iCSCs) by exogenous expression of the reprogramming transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM). The nucleosome remodeling and deacetylase (NuRD) complex is essential for reprogramming somatic cells. In this study, we investigated the function of NuRD in the induction of liver CSCs. We showed that suppression of methyl-CpG binding domain protein 3 (MBD3), a core subunit of the NuRD repressor complex, together with OSKM transduction, induces conversion of liver cancer cells into stem-like cells. Expression of the transcription factor c-JUN is increased in MBD3-depleted iCSCs, and c-JUN activates endogenous pluripotent genes and regulates iCSC-related genes. These results indicate that MBD3/NuRD inhibits the induction of iCSCs, while c-JUN facilitates the generation of CSC-like properties. The iCSC reprogramming approach devised here provides a novel platform for dissection of the disordered signaling in liver CSCs. In addition, our results indicate that c-JUN may serve as a potential target for liver cancer therapy.
authors.affiliation: Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University, Haidian District, Beijing, 100191, China.
authors.forename: Ruizhi
authors.initials: R
authors.lastname: Li
authors.affiliation: Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University, Haidian District, Beijing, 100191, China.
authors.forename: Qihua
authors.initials: Q
authors.lastname: He
authors.affiliation: Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University, Haidian District, Beijing, 100191, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Han
authors.affiliation: Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University, Haidian District, Beijing, 100191, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Beijing DongFang YaMei Gene Science and Technology Research Institute, Beijing, People's Republic of China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Liu
authors.affiliation: Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University, Haidian District, Beijing, 100191, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Su
authors.affiliation: Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University, Haidian District, Beijing, 100191, China.
authors.forename: Shiruo
authors.initials: S
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Organ Failure Research, Co-Innovation Center for Organ Failure Research, Guangdong Provincial Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University, Haidian District, Beijing, 100191, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
mesh_terms: D065150:Cellular Reprogramming; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008113:Liver Neoplasms / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C115369:MBD3 protein, human; C489427:MYC protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: C3A; MBD3/NuRD; c-JUN; induced liver cancer stem cells; transcriptional regulation