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      The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling.

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          Abstract

          Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer, and it is characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanisms underlying their self-renewal and maintenance are poorly understood. Here, using transcriptome microarray analysis, we identified a long noncoding RNA (lncRNA) termed lncTCF7 that is highly expressed in HCC tumors and liver CSCs. LncTCF7 is required for liver CSC self-renewal and tumor propagation. Mechanistically, lncTCF7 recruits the SWI/SNF complex to the promoter of TCF7 to regulate its expression, leading to activation of Wnt signaling. Our data suggest that lncTCF7-mediated Wnt signaling primes liver CSC self-renewal and tumor propagation. In sum, therefore, we have identified an lncRNA-based Wnt signaling regulatory circuit that promotes tumorigenic activity in liver cancer stem cells, highlighting the role that lncRNAs can play in tumor growth and propagation.

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          Author and article information

          Journal
          Cell Stem Cell
          Cell stem cell
          1875-9777
          1875-9777
          Apr 2 2015
          : 16
          : 4
          Affiliations
          [1 ] CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
          [2 ] Department of Hepatobiliary Surgery, PLA General Hospital, Beijing 100853, China.
          [3 ] CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
          [4 ] CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
          [5 ] CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: crs@sun5.ibp.ac.cn.
          [6 ] CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: fanz@moon.ibp.ac.cn.
          Article
          S1934-5909(15)00114-9
          10.1016/j.stem.2015.03.003
          25842979
          a4859d26-2069-4b95-9178-2cfdb5ac1454
          Copyright © 2015 Elsevier Inc. All rights reserved.
          History

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