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: Zhen-Zhen Chen, Lan Huang, Ya-Hong Wu, Wen-Jie Zhai, Ping-Ping Zhu, Yan-Feng Gao
• Journal: Nature communications (Nat Commun) Vol. 7 Pg. 12598 (08 24 2016) ISSN: 2041-1723 [Electronic] England
• PMID: 27553854 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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