title: LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression.
abstract: Liver cancer has a tendency to develop asymptomatically in patients, so most patients are diagnosed at a later stage. Accumulating evidence implicates that liver tumour-initiating cells (TICs) as being responsible for liver cancer initiation and recurrence. However, the molecular mechanism of liver TIC self-renewal is poorly understood. Here we discover that a long noncoding RNA (lncRNA) termed LncSox4 is highly expressed in hepatocellular carcinoma (HCC) tissues and in liver TICs. We find that LncSox4 is required for liver TIC self-renewal and tumour initiation. LncSox4 interacts with and recruits Stat3 to the Sox4 promoter to initiate the expression of Sox4, which is highly expressed in liver TICs and required for liver TIC self-renewal. The expression level of Sox4 correlates with HCC development, clinical severity and prognosis of patients. Altogether, we find that LncSox4 is highly expressed in liver TICs and is required for their self-renewal.
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Ya-Hong
authors.initials: YH
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Zhai
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Zhu
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.|Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, Henan Province, China.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Gao
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human