SENP1 participates in Irinotecan resistance in human colon cancer cells

• Published in: Journal of cellular biochemistry Vol. 122; no. 10; pp. 1277 - 1294
• Main Authors: Chen, Ming‐Cheng, Nhan, Do Chi, Hsu, Chiung‐Hung, Wang, Tso‐Fu, Li, Chi‐Cheng, Ho, Tsung‐Jung, Mahalakshmi, B., Chen, Mei‐Chih, Yang, Liang‐Yo, Huang, Chih‐Yang
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2021
• Subjects: Angiogenesis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chemoresistance; Colon; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Colorectal carcinoma; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; Drug resistance; Drug Resistance, Neoplasm; Gene expression; Glycolysis; HIF‐1α; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Irinotecan; Irinotecan (CPT‐11); Irinotecan - pharmacology; Protein transport; Proteins; SENP1; Signal Transduction; SUMO protein; SUMO-1 Protein - genetics; SUMO-1 Protein - metabolism; SUMOylation; Topoisomerase I Inhibitors - pharmacology; Translocation; HIF-1α; colorectal cancer; SUMOylation; drug resistance; Irinotecan (CPT-11); SENP1
• ISSN: 0730-2312; 1097-4644; 1097-4644
• DOI: 10.1002/jcb.29946

Colorectal cancer is one of the most prevalent cancers in the world. Chemoresistance has always been a problem encountered in its treatment. It is known that SUMOylation may regulate protein stability and decomposition, and even affect the protein translocation and posttranslational modification in cells. Sentrin‐specific protease 1 (SENP1) is involved in the maturation of SUMO protein, and on the other hand, plays a role in deSUMOylation, which dissociates the target protein from SUMO and prevents further degradation of the target protein. In this study, we established an Irinotecan (CPT‐11) resistant human colon cancer LoVo strain (LoVoR‐CPT‐11) to investigate the role of SENP1 in the development of drug resistance in colorectal cancer. The abundant accumulation of SENP1 and HIF‐1α proteins and the increase of SUMO pathway enzymes were observed in LoVoR‐CPT‐11 cells while the protein markers of proliferation, angiogenesis, and glycolysis were upregulated. Knockdown of SENP1 reduced the migration ability and trigged re‐sensitivity of LoVoR‐CPT‐11 cells to CPT‐11 treatment. The analysis of SENP1 and HIF‐1α gene expressions from TCGA/GTEx datasets using the GEPIA web server showed a positive correlation between SENP1 and HIF‐1α in colorectal cancer patients and the high expression of these two genes might predict a poor outcome clinically. In conclusion, SENP1 might play an important role in CPT‐11 resistance in colorectal cancer. Targeting SENP1 to reduce the resistant property could be considered in prospective clinical studies. SENP1 may regulate HIF‐1a expression in CPT‐11 resistant colon cancer cells. SENP1 is involved in the CPT‐11 resistance property in human colon cancer cells.