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LncRNAs and mRNAs expression profile in liver diseases including HCC

ABSTRACT: 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-ÎºB 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. In the study, 10 normal livers (NL), 10 chronic inflammatory livers (IL), 10 cirrhotic livers (CL), 13 early HCC (eHCC) and 13 advanced HCC (aHCC) samples were profiled their lncRNA/mRNA expression

ORGANISM(S): Homo sapiens

SUBMITTER: Jie Wang

PROVIDER: E-GEOD-54238 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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lncRNAs and mRNAs expression profile in liver diseases including HCC

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