Investigation of the relationship of C-MET signalization and lncRNA hotair in epithelial-mesenchymal transition of hepatocellular carcinoma

Objective: The aim of this study is to investigate the possible relationship between c-Met tyrosine kinase receptor and lncRNA HOTAIR in hepatocellular carcinoma (HCC). Methods: Quantitative PCR, immunoblotting, immunofluorescent staining, confocal and fluorescence imaging, real-time cell proliferation, motility and invasion analysis system, flow cytometric cell cycle analysis methods were used in the study. Results: c-Met expression and activation, HOTAIR expression levels were determined in HCC cell lines and an inverse correlation was found between HOTAIR expression and c-Met activation. In this study, ligand-dependent and independent c- Met activation in HCC cells suppresses HOTAIR expression and, inhibition of c-Met tyrosine kinase activity reverses HOTAIR expression. HOTAIR knock down increased gene expression of c-Met and Caveolin-1 which is a scaffolding protein which activates c-Met signaling ligand independently. HOTAIR overexpression in HCC cells supress c- Met and Caveolin-1 expression and activation. HOTAIR inhibits the activation of Src kinase and Erk1/2 kinases involved in c-Met transduction; and reduce motility, invasion and proliferation. HOTAIR overexpression contributes to the adhesion-independent survival of HCC cells by reducing expression of cell tp ECM adhesion molecules. Conclusion: In conclusion, the thesis study described the c-Met/Caveolin- 1/HOTAIR molecular reciprocal interaction and its function in HCC for the first time. Key words: HCC, lncRNA, Caveolin-1, c-Met