LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression

Zhen-Zhen Chen; Lan Huang; Ya-Hong Wu; Wen-Jie Zhai; Ping-Ping Zhu; Yan-Feng Gao

doi:10.1038/ncomms12598

LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression

Nat Commun. 2016 Aug 24:7:12598. doi: 10.1038/ncomms12598.

Authors

Zhen-Zhen Chen¹, Lan Huang², Ya-Hong Wu¹, Wen-Jie Zhai¹, Ping-Ping Zhu³, Yan-Feng Gao^{1

4}

Affiliations

¹ School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
² The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
³ School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
⁴ Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001, Henan Province, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism*
Carcinoma, Hepatocellular / pathology*
Cell Line, Tumor
Cell Self Renewal / genetics
Cell Transformation, Neoplastic / genetics
Humans
Liver Neoplasms / genetics
Liver Neoplasms / metabolism*
Liver Neoplasms / pathology*
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Recurrence, Local / genetics
Neoplasm Recurrence, Local / metabolism
Neoplasm Recurrence, Local / pathology
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / pathology*
Prognosis
Promoter Regions, Genetic
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism*
RNA, Neoplasm / genetics
RNA, Neoplasm / metabolism
SOXC Transcription Factors / genetics*
SOXC Transcription Factors / metabolism
STAT3 Transcription Factor / metabolism*
Transcriptome

Substances

RNA, Long Noncoding
RNA, Neoplasm
SOX4 protein, human
SOXC Transcription Factors
STAT3 Transcription Factor
STAT3 protein, human