title: lnc-β-Catm elicits EZH2-dependent β-catenin stabilization and sustains liver CSC self-renewal.
abstract: Liver cancer stem cells (CSCs) may contribute to the high rate of recurrence and heterogeneity of hepatocellular carcinoma (HCC); however, the molecular mechanisms underlying their self-renewal and differentiation remain largely unknown. Through analysis of transcriptome microarray data, we identified a long noncoding RNA (lncRNA) called lnc-β-Catm, which is highly expressed in human HCC tumors and liver CSCs. We found that lnc-β-Catm is required for self-renewal of liver CSCs and tumor propagation in mice. lnc-β-Catm associates with β-catenin and the methyltransferase EZH2, thereby promoting β-catenin methylation. Methylation suppresses the ubiquitination of β-catenin and promotes its stability, thus leading to activation of Wnt-β-catenin signaling. Accordingly, the expression of lnc-β-Catm, EZH2 and Wnt-β-catenin targets is positively correlated with cancer severity and prognosis of people with HCC.
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yanying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Guanling
authors.initials: G
authors.lastname: Huang
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Buqing
authors.initials: B
authors.lastname: Ye
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Benyu
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Hepatobiliary Surgery, PLA General Hospital, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Zusen
authors.initials: Z
authors.lastname: Fan
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D059467:Transcriptome; D054875:Ubiquitination; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D051176:beta Catenin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein