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.
Highlights
Liver cancer has a tendency to develop asymptomatically in patients, so most patients are diagnosed at a later stage
We proved that the Stat3–Sox[4] pathway participates in liver tumorigenesis and liver tumour-initiating cells (TICs) self-renewal, offering a new potential target of TICs for eradicating liver cancer
Top 100 long noncoding RNA (lncRNA) were selected and a heatmap was generated (Fig. 1a). We analysed another patient cohort, Li’s cohort (GSE40144, microarray data of genes and lncRNAs, with disease-free survival and overall survival information of 59 hepatocellular carcinoma), and found hundreds of lncRNAs related to HCC severity and prognosis
Summary
Liver cancer has a tendency to develop asymptomatically in patients, so most patients are diagnosed at a later stage. We discover that a long noncoding RNA (lncRNA) termed LncSox[4] is highly expressed in hepatocellular carcinoma (HCC) tissues and in liver TICs. We find that LncSox[4] is required for liver TIC self-renewal and tumour initiation. LncSox[4] interacts with and recruits Stat[3] to the Sox[4] promoter to initiate the expression of Sox[4], which is highly expressed in liver TICs and required for liver TIC self-renewal. We discovered a long noncoding RNA termed LncSox[4] initiates liver TIC self-renewal through Stat3–Sox[4] pathway. LncSox[4] interacts with and recruits Stat[3] to Sox[4] promoter, initiating Sox[4] expression and liver TIC self-renewal. We proved that the Stat3–Sox[4] pathway participates in liver tumorigenesis and liver TIC self-renewal, offering a new potential target of TICs for eradicating liver cancer
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