lncRNAs and mRNAs expression profile in liver diseases including HCC

Sustained hepatic inflammation can contribute to cancer initiation and progression via tumor-initiating cell expansion, but underlying mechanisms remains unknown. Expression profiles of lncRNAs/mRNAs were measured in normal, chronic hepatitis, cirrhotic and cancerous livers. We found abundant disease-related lncRNAs/mRNAs deregulated across different stages of inflammation-triggered liver disease and refined a transformation gene signature to distinguish pathological liver tissues. Amongst this signature, a conserved lncRNA DANCR was silenced in normal adult liver, but overexpressed in fetal and cancerous livers. Remarkably, increased DANCR significantly correlates with poor prognosis in multiple-center cohorts and is directly induced by inflammatory pathways including NF-κB and STAT3. DANCR could suppress cell differentiation and drive expansion of tumor-initiating cells, leading to chemoresistance. Moreover, in vitro and in vivo inhibition confirms the significance of DANCR as a therapeutic target when combined with other chemotherapy. We illustrate the role of DANCR relies on the regulation of CTNNB1 in a novel miRNA-blocking manner. Our studies reveal the expression of lncRNAs/mRNAs in normal and pathological livers and suggest the importance of oncofetal lncRNA DANCR in inflammation-induced malignant transformation, offering a potential prognostic marker and a therapeutic target for HCC.