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
Affiliations
Weitao Shen
Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, People’s Republic of China
Peng Luo
Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, People’s Republic of China
Yueqin Sun
Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, People’s Republic of China
Wei Zhang
Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, People’s Republic of China
Ningning Zhou
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
Hongrui Zhan
Department of Rehabilitation, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong, People’s Republic of China
Qingxi Zhang
The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, People’s Republic of China
Jie Shen
Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, People’s Republic of China
Anqi Lin
Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, People’s Republic of China
Quan Cheng
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of China
Qiongyao Wang
Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, People’s Republic of China
Jian Zhang
Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, People’s Republic of China; Corresponding author
Hai-Hong Wang
Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, People’s Republic of China; Corresponding author
Ting Wei
Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, People’s Republic of China; Corresponding author
Summary: 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.
