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Research Paper|Volume 12, Issue 16|pp 16390—16409

PRDX2 removal inhibits the cell cycle and autophagy in colorectal cancer cells

Xiangru Zheng1, Jinlai Wei1, Wenjun Li2, Xiaoli Li3, Wuyi Wang1, Jinbao Guo4, Zhongxue Fu1
  • 1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 2Department of Pharmacy, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 3College of Pharmacy, Chongqing Medical University, Chongqing, China
  • 4Department of Thoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Received: December 21, 2019Accepted: June 29, 2020Published: July 20, 2020
https://doi.org/10.18632/aging.103690

Copyright © 2020 Zheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Colorectal cancer (CRC) is a prevalent worldwide disease in which the antioxidant enzyme peroxiredoxin 2 (PRDX2) plays an important role. To investigate the molecular mechanism of PRDX2 in CRC, we performed bioinformatics analysis of The Cancer Genome Atlas (TCGA) datasets and Gene Expression Omnibus (GEO) DataSets (accession no. GSE81429). Our results suggest that PRDX2 is associated with cell-cycle progression and autophagy activated by the P38 MAPK/FOXO signaling pathway. Using a short-hairpin RNA vector, we verified that PRDX2 is essential for CRC cell proliferation and S-phase progression. Immunostaining, electron microscopy and western blotting assays verified the effect of PRDX2 knockdown on autophagy flux and p38 activation. The P38 activator dehydrocorydaline chloride partially rescued the effects of sh-PRDX2 on the expression of proteins related to cell-cycle progression and autophagy. We verified the correlation between PRDX2 expression and the expression of an array of cell-cycle and autophagy-related genes using data from an independent set of 222 CRC patient samples. A mouse xenoplast model was consistent with in vitro results. Our results suggest that PRDX2 promotes CRC cell-cycle progression via activation of the p38 MAPK pathway.