NRBF2 regulates the chemoresistance of small cell lung cancer by interacting with the P62 protein in the autophagy process

Weitao Shen; Peng Luo; Yueqin Sun; Wei Zhang; Ningning Zhou; Hongrui Zhan; Qingxi Zhang; Jie Shen; Anqi Lin; Quan Cheng; Qiongyao Wang; Jian Zhang; Hai-Hong Wang; Ting Wei

doi:10.1016/j.isci.2022.104471

NRBF2 regulates the chemoresistance of small cell lung cancer by interacting with the P62 protein in the autophagy process

iScience. 2022 May 26;25(6):104471. doi: 10.1016/j.isci.2022.104471. eCollection 2022 Jun 17.

Authors

Weitao Shen¹, Peng Luo¹, Yueqin Sun¹, Wei Zhang¹, Ningning Zhou², Hongrui Zhan³, Qingxi Zhang⁴, Jie Shen¹, Anqi Lin¹, Quan Cheng⁵, Qiongyao Wang¹, Jian Zhang¹, Hai-Hong Wang⁶, Ting Wei¹

Affiliations

¹ Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, People's Republic of China.
² Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510282, Guangdong, People's Republic of China.
³ Department of Rehabilitation, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, People's Republic of China.
⁴ The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
⁵ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People's Republic of China.
⁶ Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.

Abstract

Reversing chemotherapy resistance in small cell lung cancer (SCLC) is crucial to improve patient prognosis. The present study aims to investigate the underlying mechanisms in SCLC chemoresistance. We see that nuclear receptor binding factor 2 (NRBF2) is a poor prognostic factor in SCLC. The effects of NRBF2 on chemoresistance were determined in SCLC. The underlying molecular mechanisms of NRBF2 in the autophagy process in SCLC were examined. NRBF2 positively regulated autophagy, leading to drug resistance in SCLC. The MIT domain of NRBF2 directly interacted with the PB1 domain of P62. This interaction increased autophagic P62 body formation, revealing the regulatory role of NRBF2 in autophagy. Notably, NRBF2 was directly modulated by the transcription factor XRCC6. The MIT domain of NRBF2 interacts with the PB1 domain of P62 to regulate the autophagy process, resulting in SCLC chemoresistance. NRBF2 is likely a useful chemotherapy response marker and therapeutic target in SCLC.

Keywords: Cancer; Cell biology.