PO-144 HGF/c-met signalling pathway downregulates lncRNA HOTAIR to induce adhesion independent growth in HCC by increasing caveolin-1 expression

Introduction c-Met pathway is important in the development of hepatocellular carcinoma (HCC) and elevated expression is correlated with metastasis, poor prognosis, and drug resistance.c-Met activation in HCC is a critical phenomenon and became an important molecular target of hepatocellular carcinoma therapies.HOTAIR expression is defined to be upregulated in various cancer types and linked to poor prognosis and aggressive cancer phenotype.Elevated expression of HOTAIR in HCC tissues, its relation with cancer stem cell phenotype, poor prognosis and metastasis lead us to investigate its possible link between HOTAIR and c-Met. Material and methods Gene mRNA and protein expressions were analysed by qPCR and western blot. Biological responses of the cells were analysed with wound healing assay, invasion assay and circulating experiments were performed with an experimental setup with a peristaltic pump. Results and discussions In our studies, HOTAIR expression is found to be reversely correlated with c-Met expression and activation in HCC cell lines, for the first time.c-Met activation leads to down-regulation of lncRNA HOTAIR expression and also, inhibition of c-Met activation recovers HOTAIR expression. c-Met pathway is defined to be activated in ligand-dependent and independent manner. Reciprocal interaction of c-Met and HOTAIR was conserved in ligand-independent c-Met activation,too.Bioinformatics analysis of HOTAIR regulated genes highlighted some genes that are known to contribute to c-Met pathway via enabling its activation.The possible molecules that take part in reciprocal interaction of c-Met and HOTAIR are analysed by qPCR and western blot. Our findings are the first to show Caveolin-1, a membrane protein, is an important target of HOTAIR to regulate c-Met pathway and also Vimentin is regulated by HOTAIR expression to mediate epithelial/mesenchymal phenotype in HCC.To further understand the role of HOTAIR and c-Met interaction in metastasis; expression of HOTAIR, c-Met and related molecules were analysed in circulating HCC cells under shear stress. Conclusion Reported data revealed that c-Met pathway related mesenchymal phenotype and adhesion-independent cell growth requires HOTAIR downregulation which leads to increase of Caveolin-1 expression.Here we report that HOTAIR downregulation is a requirement to survive in circulation, adhesion independent survival and growth and it is regulated by c-Met receptor tyrosine kinase activity.Our results contribute to the literature by mapping the interaction of HOTAIR and c-Met.