The Study On MARVELD1Expression And Effect On Cell Proliferation And Migration In Pancreatic Cancer

Pancreatic cancer is a deadly malignancy with high mortality and poor survival.Until today the effective treatments are still few. Therefore the study of molecularmechanism is attractive. MARVELD1(MARVEL domain containing1) gene is acandidate tumor suppressor gene discovered by our laboratory previously. It is downregulated in many cancers such as breast and lung cancer. The epigenetic modificationmay play an importent role in its down-regulation. MARVELD1has also discoveredfunctions like proliferation inhibition and cell cycle arrest.To study MARVELD1in pancreatic cancer, we firstly analyzed MARVELD1expression in31pancreatic cancer cases, using Immunohistochemcal staining. ThenWestern Blot and quantitative Real-time PCR were used to observe mRNA and proteinexpression of MARVELD1in pancreatic cancer cells. The results show thatMARVELD1expression in cancer tissues is obviously lower than control, especially inearly stage. And two in three pancreatic cancer cell lines express low level ofMARVELD1.In order to investigate the epigenetic factors related to MARVELD1expression, wechose two drugs for the analysis, which are DNA methylation inhibitor5-Aza-CdR andhistone deacetylase inhibitor (HDACi) TSA. The results show that5-Aza-CdR and TSAtreatment can both up-regulate mRNA and protein expression of MARVELD1, and leadto obviously increment when both offered to pancreactic cancer cells. It suggests thatDNA methylation and histone acetylation are related to MARVELD1expression.At last, for further analysis of MARVELD1on cell ability, pancreatic cancer cellswith over expressed MARVELD1were built for experiments. The results show thatcells transfected MARVELD1was weaker in proliferation and migration than control,suggesting that MARVELD1inhibit cell proliferation and migration.All above, the study indicated that MARVELD1is down-regulated in pancreaticcancer tissues and cells, which is related to DNA methylation accompanied with histoneacetylation. And the down-regulation of MARVELD1promotes cell proliferation andmigration.