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

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

Xiangru Zheng, Jinlai Wei, Wenjun Li, Xiaoli Li, Wuyi Wang, Jinbao Guo and Zhongxue Fu
Aging (Albany, NY.), Vol.12(16), pp.16390-16409
20/07/2020
PMID: 32692719

Abstract

Animals Autophagy Autophagy-Related Proteins - genetics Autophagy-Related Proteins - metabolism Cell Cycle Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Proliferation Colorectal Neoplasms - enzymology Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Databases, Genetic Enzyme Activation Female Forkhead Transcription Factors - metabolism Gene Expression Regulation, Neoplastic HCT116 Cells HT29 Cells Humans Mice, Inbred BALB C Mice, Nude p38 Mitogen-Activated Protein Kinases - metabolism Peroxiredoxins - genetics Peroxiredoxins - metabolism Phosphorylation Signal Transduction
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. ). 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 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.

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