MBD3 inhibits formation of liver cancer stem cells
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Ruizhi Li1, Qihua He1, Shuo Han1, Mingzhi Zhang1, Jinwen Liu2, Ming Su1, Shiruo Wei1, Xuan Wang3, Li Shen1
1Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University, Haidian District, Beijing, 100191, China
2Beijing DongFang YaMei Gene Science and Technology Research Institute, Beijing, People’s Republic of China
3State 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
Li Shen, email: [email protected]
Keywords: induced liver cancer stem cells, MBD3/NuRD, c-JUN, C3A, transcriptional regulation
Received: July 28, 2016 Accepted: October 19, 2016 Published: November 22, 2016
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.
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