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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1381860
This article is part of the Research Topic The Molecular Mechanism in Anti-tumor Therapy Resistance View all articles

RREB1-mediated SUMOylation enhancement promotes chemoresistance partially by transcriptionally upregulating UBC9 in colorectal cancer

Provisionally accepted
Ya-nan Deng Ya-nan Deng 1Ying Chen Ying Chen 2Shan Gao Shan Gao 1Nan Zhang Nan Zhang 1Yinheng Luo Yinheng Luo 1Shu Luo Shu Luo 2Qiu Li Qiu Li 1Xianghui Fu Xianghui Fu 1Shufang Liang Shufang Liang 1*
  • 1 Sichuan University, Chengdu, Sichuan Province, China
  • 2 Suining First People's Hospital, Suining, Sichuan Province, China

The final, formatted version of the article will be published soon.

    Chemoresistance is a main cause of chemotherapy failure and tumor recurrence.The effects of global protein SUMOylation on chemoresistance in colorectal cancer (CRC) remains to be investigated. Herein, we have proposed that the elevated SUMO2/3-modified proteins confer 5-fluorouracil (5-FU) chemoresistance acquisition in CRC. The SUMOylation levels of global proteins in CRC cell lines were elevated compared with normal colon cell line NCM460. 5-FU treatment obviously reduced SUMOylation of global proteins in 5-FU-sensitive CRC cells including HT29, HCT116 and HCT-8. However, in 5-FU-resistant HCT-8/5-FU cells, the expression level of SUMO2/3-modified proteins was increased under 5-FU exposure in a concentration-dependent manner. 5-FU treatment combined with SUMOylation inhibitor ML-792 significantly increased the sensitivity of 5-FUresistant cells to 5-FU and reduced colony formation numbers in HCT-8/5-FU cells.And UBC9-mediated SUMOylation elevation contributes to 5-FU resistance in HCT116 cells. Moreover, we also identified RREB1 as a regulator of SUMOylation profiling of global cellular proteins via directly binding to the promoter of UBC9.Overexpression of RREB1 promoted 5-FU resistance in CRC, which was partially abolished by treatment of inhibitor ML-792. In conclusion, RREB1-enhanced protein SUMOylation contributes to 5-FU resistance acquisition in CRC.

    Keywords: Sumoylation, colorectal cancer, chemoresistance, 5-FU, RREB1, Ubc9

    Received: 04 Feb 2024; Accepted: 10 Jul 2024.

    Copyright: © 2024 Deng, Chen, Gao, Zhang, Luo, Luo, Li, Fu and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Shufang Liang, Sichuan University, Chengdu, 610065, Sichuan Province, China

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