KIAA1199 promotes oxaliplatin resistance and epithelial mesenchymal transition of colorectal cancer via protein O-GlcNAcylation

Qingling Hua; Yuanyuan Lu; Dingxiang Wang; Jie Da; Wanren Peng; Guoping Sun; Kangsheng Gu; Hua Wang; Yanzhe Zhu

doi:10.1016/j.tranon.2023.101617

KIAA1199 promotes oxaliplatin resistance and epithelial mesenchymal transition of colorectal cancer via protein O-GlcNAcylation

Transl Oncol. 2023 Feb:28:101617. doi: 10.1016/j.tranon.2023.101617. Epub 2023 Jan 5.

Authors

Qingling Hua¹, Yuanyuan Lu², Dingxiang Wang³, Jie Da¹, Wanren Peng¹, Guoping Sun¹, Kangsheng Gu¹, Hua Wang¹, Yanzhe Zhu⁴

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China.
² Department of Radiation Oncology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241004, China.
³ Department of Psychology, The fourth people's hospital, Wuhu, 241003, China.
⁴ Department of Oncology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, China. Electronic address: zhuyanzhe@ahmu.edu.cn.

Abstract

Oxaliplatin is a commonly used platinum drug for colorectal cancer (CRC). However, the treatment of CRC by oxaliplatin usually fails because of drug resistance, which results in a huge challenge in the therapy of CRC. Elucidation of molecular mechanisms may help to overcome oxaliplatin resistance of CRC. In our study, we revealed that KIAA1199 can promote oxaliplatin resistance of CRC. Mechanistically, KIAA1199 prevents oxaliplatin mediated apoptosis via up-regulated PARP1 derived from reduced endoplasmic reticulum stress induced by protein O-GlcNAcylation. In the meantime, KIAA1199 can also trigger epithelial mesenchymal transition by stabilizing SNAI1 protein via O-GlcNAcylation. Therefore, KIAA1199 has great potential to be a novel biomarker, therapeutic target for oxaliplatin resistance and metastasis of CRC.

Keywords: EMT; Endoplasmic reticulum stress; KIAA1199; O-GlcNAcylation; PARP1; SNAI1.