Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Department of Medical Examination, Xiamen International Travel Healthcare Center, Xiamen 361000, Fujian, China.
Int J Biochem Cell Biol. 2022 Jun;147:106233. doi: 10.1016/j.biocel.2022.106233. Epub 2022 Jun 1.
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.
结直肠癌是一种起始于结直肠黏膜上皮的恶性肿瘤。NPM1 是一种核仁磷酸化蛋白，与人类肿瘤的进展有关。NPM1 在多种肿瘤中均显著过表达，包括结直肠癌，但它在结直肠癌中的作用和机制尚不清楚。因此，本研究旨在通过 PRDX6 发现 NPM1 促进结直肠癌细胞增殖的作用及其分子机制。根据我们的发现，NPM1 的敲低或过表达分别抑制或促进了 HCT-116 和 HT-29 结直肠癌细胞的增殖和细胞周期进程。此外，NPM1 的敲低或过表达增加或降低了细胞内 ROS 水平。动物实验表明，NPM1 的敲低或过表达抑制或促进了皮下移植的结直肠癌细胞的生长。根据我们的发现，NPM1 的敲低或过表达分别降低或增加了 PRDX6 的表达和相关酶活性。免疫沉淀证实了 NPM1 与 CBX3 形成复合物，双荧光素酶报告基因检测证实 CBX3-NPM1 复合物促进了 PRDX6 的转录。我们的数据支持了 NPM1 促进结直肠癌细胞增殖的作用，这可能是通过 CBX3 促进抗氧化蛋白 PRDX6 的表达，从而抑制细胞内 ROS 水平来实现的。NPM1 和 PRDX6 是潜在的结直肠癌治疗靶点。
