P53-induced MRVI1 mediates carcinogenesis of colorectal cancer

Abstract

Background: Colorectal cancer (CRC) is one of the most prevalent cancer types worldwide. Despite the advancements in current diagnosis and treatment strategies of CRC, the incidence and mortality rates of CRC have been rising. To explore novel mechanism of CRC, this study focused on the expression pattern and functional mechanism of murine retrovirus integration site 1 (MRVI1) in CRC.Methods: Tumor tissues and adjacent normal tissues were collected from CRC patients, and the expression levels of MRVI1 were determined by RT-PCR and Western blot. MRVI1 knockdown was achieved by shRNA in HCT116 and HT29 cells, followed by CCK-8 assay to detect the cell proliferation, and caspase-3 activity assay combined with nucleosome ELISA assay to detect cell apoptosis. Transwell assay was used to detect cell invasion and luciferase reporter assay was used to validate the activation of the MRVI1 promoter by p53.Results: MRVI1 was downregulated in CRC tissues and several CRC cell lines. Knockdown of MRVI1 enhanced the proliferation and apoptosis, while promoted invasion and stemness of CRC cells. Mechanism study revealed that MRVI1 was transcriptionally activated by p53 at its upstream. In addition, p53-induced inhibition of CRC prognosis depended on MRVI1.Conclusion: MRVI1 inhibited the prognosis of CRC via a mechanism involving p53 activation. MRVI1 could serve as a potential target for clinical diagnosis and treatment of CRC.