Malt1 parakaspazın (mucosa-assocıated lymphoıd tıssue lymphoma translocatıon proteın 1) hepatoselüler karsinom hücre sağkalımı üzerındekı rolünün araştırılması

Hepatocellular carcinoma (HCC) is a leading cause of cancer related deaths around the world and is associated with several etiological factors including infections with hepatitis B and C viruses, heavy alcohol consumption and chronic aflatoxin B1 exposure. Treatment strategies for HCC are currently limited. Hepatocarcinogenesis process involves alterations in several molecular pathways including activation of NF-κB pathway. MALT1 (Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1) is a cytosolic signaling molecule which acts both as a scaffold protein and as a protease for NF-κB pathway activation. To date, the contribution of MALT1 to HCC cell survival has not been studied. In the present study, we investigated the effects of MALT1 inhibition on HCC cell survival. For this purpose, we depleted the MALT1 levels in HCC cell lines via three strategies; RNAi, CRISPR-Cas9 and small molecule inhibitor and we analyzed the cell survival with different methods. Based on the preliminary results, shRNA-mediated gene silencing or pharmacological inhibition with MI-2 reduced cell growth in vitro, and this decrease in cell growth is associated with inhibition of cell proliferation as well as reduced expression of well-known NF-kB downstream targets, an indirect indication of NF-κB pathway inactivation. Besides, we employed a competition assay using CRISPR-Cas9 system to test for MALT1 dependency in HCC cells. Conclusively, our results suggest that MALT1 plays an important role in HCC cell growth. Further studies focusing on delineating the molecular mechanisms underlying the growth regulating effects of MALT1 are currently underway. By all means, we think that pharmacological inhibition of MALT1 in HCC is a promising avenue to be explored further.