Potential Role Of DHX33 In The Development Of Human Colon Cancer

Colon cancer(CRC)is one of the most common malignancies in the world.Every year colon cancer-related death rate remains high,but there is no effective therapeutic treatment for it up to now.Previous studies of our lab provided evidence that RNA helicase DHX33 is a major regulator in cell proliferation and growth.It was found to be highly expressed in several human cancers.However,it remains unknown whether DHX33 plays a role in colon cancers,if it does,what would be the exact role of DHX33 in colon cancer? In this study,DHX33 was knocked down in HCT116 and LOVO cells by lentiviral delivery of shRNAs.Western blot and Real-time quantitative polymerase chain reaction(RT qPCR)were performed to detect the expression levels of a set of critical genes involved in cell cycle,apoptosis and cell migration.Additionally,cell proliferation assay,cell colony formation assay,cell apoptosis analysis were performed to elucidate the role of DHX33 in CRC development and progression.Our findings strongly suggest that DHX33 is highly expressed in colon cancer tissues and colon cancer cell lines;knockdown of DHX33 significantly decreased cell proliferation and promoted cell apoptosis.Mechanistically,DHX33 transcriptionally controls critical genes involved in cell cycle,apoptosis and migration.Importantly,DHX33 deficiency inhibited tumor growth of colon cancer cells in a xenograft model in vivo.Deregulation of the Wnt/β-catenin signaling is frequently detected in colon cancer.To investigate the molecular mechanism for DHX33 regulation in colon cancer,we used Wnt/β-catenin activator,recombinant human Wnt3 a protein,and Wnt inhibitor,DKK1,to treat HCT116 cells.We also used LiCl to perturb Wnt signaling in this system,and then analyzed DHX33 expression.Our findings suggest that DHX33 and Wnt/β-catenin signaling pathway have reciprocal regulation.In addition,GSK3β might directly regulate DHX33 in a Wnt independent manner.This study for the first time demonstrates the role of DHX33 in colon cancer and the underlying molecular mechanism.Researches also provide the initial report for the relationship between DHX33 and Wnt/β-catenin signaling pathway as well as DHX33 and GSK3β in colon cancers.This may provide new therapeutic target for treating colon cancer.The findings may shed light on a novel way for the treatment of colon cancers.