Enforced expression of RASAL1 suppresses cell proliferation and the transformation ability of gastric cancer cells

RAS protein activator like 1 (RASAL1) is a member of the RAS GTPase-activatingprotein (GAP) family, and it is an important molecule in the regulation of RASactivation. In the present study, we investigated the role of RASAL1 in gastriccarcinogenesis. Decreased expression pattern of RASAL1 in gastric cancer tissuesand cell lines was found in protein and RNA levels, although there was no statisticallysignificant relationship between RASAL1 and clinicopathological features. Restoredexpression of RASAL1 induced by DNA methylation inhibitor 5-aza-2'-deoxycytidine(5'-AZA) and HDAC inhibitor trichostatin A (TSA) implied that RASAL1 expressionis regulated by epigenetic mechanisms. The biological role of RASAL1 in gastriccarcinogenesis was determined by in vitro tumorigenicity assays. Overexpressionof RASAL1 showed suppression of cell proliferation due to cell apoptosis. Subsequently,enforced expression of RASAL1 repressed significantly the gastric cancer celltransformation ability. These findings demonstrated that decreased RASAL1 expressionis a characteristic of gastric cancer and regulated by epigenetic mechanisms.RASAL1 may be a functional tumor suppressor involved in gastric cancer. This studyprovides novel insights into the biological role of RASAL1 in gastric carcinogenesis.