Downregulation of transcription factor EB inhibits the growth and metastasis of colorectal carcinomas

Abstract

To determine the roles of transcription factor EB (TFEB) in colorectal cancer (CRC), we collected samples of tumor tissues and normal tissues from 40 patients with CRC. The expression of TFEB in these samples was analyzed by using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Furthermore, we explored the expression of TFEB mRNA in CCD-18Co normal cells and HT-29, HCT-8, C2BBe1 cancer cells. HT-29, HCT-8, and C2BBe1 cancer cells were transfected with a TFEB-specific small interference RNA (siRNA) and scrambled siRNA, then the TFEB expression was confirmed by Western blot. The migration and invasion abilities of cells transfected with TFEB-siRNA were examined by transwell method and wound-healing assay. The subsequent effect of TFEB silencing on the tumor growth was also detected in mice xenograft model in vivo. Our study found that TFEB expression was significantly increased ( P < 0.05) in colorectal tumor tissues compared with normal tissues. Consistent with TFEB expression in tissues, compared with the normal CCD-18Co cells, TFEB mRNA expression was also significantly augmented in CRC cells. TFEB protein expression was markedly reduced in HT-29, HCT-8, and C2BBe1 cells after TFEB-siRNA transfection. In addition, inhibition of TFEB expression resulted in decrease of cells migration and invasion abilities. In vivo study, compared with the negative control group, the tumor weight, and volume were also reduced after inhibiting the TFEB expression. Our research suggested that TFEB expression is related to the occurrence and development of colorectal adenocarcinoma. The migration and invasion abilities of cancer cells, the weight and volume of tumor were all decreased when inhibiting TFEB expression. Thus, TFEB serves as an important factor in the development of CRC by modulating cancer cell migration and invasion, showing the potential therapeutic target of CRC in clinical.