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Vol 57(2023) N 6 p. 1228-1238; DOI 10.1134/S0026893324010175  Y.W. Wang1, K.G. Jia2, H.J. Xing3, Y. Pan4, C.S. Zeng3, L. Chen3, Q.J. Su3, W.T. Shen5, J. Chen6, C. Chen3*, Q. Cao7, Y.Y. Wang2** Interaction of SENP6 with PINK1 Promotes Temozolomide Resistance in Neuroglioma Cells via Inducing the Mitophagy 1School of Medicine of University of Electronic Science and Technology of China, Chengdu, 611730 People's Republic of China2Department of Thoracic Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610031 People's Republic of China 3Department of Neurology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, 570100 People's Republic of China 4Department of Pharmacy, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, 570100 People's Republic of China 5Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510280 People's Republic of China 6Department of Neurology, Danzhou People's Hospital, Danzhou, Hainan Province, 571700 People's Republic of China 7Department of Assisted Reproductive Medicine, Sichuan Provincial Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 611730 People's Republic of China *315chencong@163.com **Wangyouyu121@163.com Received - 2023-03-05; Revised - 2023-05-09; Accepted - 2023-05-19 Temozolomide resistance is a major cause of recurrence and poor prognosis in neuroglioma. Recently, growing evidence has suggested that mitophagy is involved in drug resistance in various tumor types. However, the role and molecular mechanisms of mitophagy in temozolomide resistance in glioma remain unclear. In this study, mitophagy levels in temozolomide-resistant and -sensitive cell lines were evaluated. The mechanisms underlying the regulation of mitophagy were explored through RNA sequencing, and the roles of differentially expressed genes in mitophagy and temozolomide resistance were investigated. We found that mitophagy promotes temozolomide resistance in glioma. Specifically, small ubiquitin-like modifier specific protease 6 (SENP6) promoted temozolomide resistance in glioma by inducing mitophagy. Protein-protein interactions between SENP6 and the mitophagy executive protein PTEN-induced kinase 1 (PINK1) resulted in a reduction in small ubiquitin-like modifier 2 (SUMO2)ylation of PINK1, thereby enhancing mitophagy. Our study demonstrates that by inducing mitophagy, the interaction of SENP6 with PINK1 promotes temozolomide resistance in glioblastoma. Therefore, targeting SENP6 or directly regulating mitophagy could be a potential and novel therapeutic target for reversing temozolomide resistance in glioma. glioblastoma, temozolomide resistance, SENP6, mitophagy, PINK1 |
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