NPM1 promotes cell proliferation by targeting PRDX6 in colorectal cancer

Abstract

Colorectal cancer is a malignant tumor that begins in the colorectal mucosal epithelium. NPM1 is a nucleolar phosphoprotein that has been linked to tumor progression in humans. NPM1 is significantly overexpressed in a variety of tumors, including colorectal cancer, but its role and mechanism in colorectal cancer remain unknown. Therefore, the purpose of this study was to discover the role of NPM1 in promoting colorectal cancer proliferation via PRDX6 and its molecular mechanism. NPM1 knockdown or overexpression inhibited or promoted the proliferation and cell cycle progression of HCT-116 and HT-29 colorectal cancer cells, respectively, according to our findings. Furthermore, NPM1 knockdown or overexpression increased or decreased intracellular ROS levels. Animal experiments revealed that NPM1 knockdown or overexpression inhibited or promoted the growth of colorectal cancer cells transplanted subcutaneously. NPM1 knockdown or overexpression reduced or increased PRDX6 expression and related enzyme activities, respectively, according to our findings. NPM1 formed a complex with CBX3 as evidenced by immunoprecipitation, and the double luciferase reporter gene assay confirmed that the CBX3-NPM1 complex promoted PRDX6 transcription. Our data support the role of NPM1 in promoting the proliferation of colorectal cancer, which may be accomplished by CBX3 promoting the expression of the antioxidant protein PRDX6 and thus inhibiting intracellular ROS levels. NPM1 and PRDX6 are potential colorectal cancer therapeutic targets.

Keywords: Colorectal cancer; Nucleophosmin; PRDX6.