The Epigenetic Changes Of TMEM176A And The Function And Mechanism Study In Colorectal Cancer

Colorectal cancer(CRC) is the third most common malignancies and the fourth most common cause of cancer related death in the world. The incidence is increasing fast in China. The accumulation of genetic and epigenetic alterations may drive carcinogenesis and progression in CRC. Aberrant DNA methylation is considered as a hallmark of cancers. The differentially expressed genes were isolated by RNA-sequencing and TMEM176 A was identified apparently reduced expression in CRC. To study the role of TMEM176 A in human colorectal cancer, eight colorectal cancer cell lines, 96 cases of primary colorectal cancer samples were used. MSP,BSSQ, RT-PCR, IHC, MTT, gene expression array, flow Cytometry, transwell assay and xenograft mice model were employed. The results suggest that the expression of TMEM176 A was regulated by promoter regional methylation in colorectal cancer cells. TMEM176 A was methylated in 53.13% of primary colorectal cancers and TMEM176 A methylation was associated with tumor metastasis(p < 0.05).Restoration of TMEM176 A expression suppressed CRC cells growth both in vitro and in vivo. TMEM176 A induced apoptosis and inhibited cell migration and invasion in CRC cells. The expression levels of 394 genes were changed before and after restoration of TMEM176 A expression in DLD1 cells, among which 170 genes were up-regulated and 224 genes were down-regulated. In conclusion, the expression of TMEM176 A was regulated by promoter regional methylation. TMEM176 A methylation is associated with CRC metastasis. TMEM176 A induced apoptosis in colorectal cancer cells and inhibited CRC growth and metastasis both in vitro and in vivo.