单位：[1]Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy, West Lafayette, Indiana, USA[2]Department of Gastroenterology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China内科学系消化内科华中科技大学同济医学院附属同济医院[3]College of Chemical Engineering, Sichuan University of Science & Engineering, Zigong, China
Background: In response to therapeutic treatments, cancer cells can exhibit a variety of resistance phenotypes including neuroendocrine differentiation (NED). NED is a process by which cancer cells can transdifferentiate into neuroendocrine-like cells in response to treatments, and is now widely accepted as a key mechanism of acquired therapy resistance. Recent clinical evidence has suggested that non-small cell lung cancer (NSCLC) can also transform into small cell lung cancer (SCLC) in patients treated with EGFR inhibitors. However, whether chemotherapy induces NED to confer therapy resistance in NSCLC remains unknown.Methods: We evaluated whether NSCLC cells can undergo NED in response to chemotherapeutic agents etoposide and cisplatin. By Knock-down of PRMT5 or pharmacological inhibition of PRMT5 to identify its role in the NED process.Results: We observed that both etoposide and cisplatin can induce NED in multiple NSCLC cell lines. Mechanistically, we identified protein arginine methyltransferase 5 (PRMT5) as a critical mediator of chemotherapy-induced NED. Significantly, the knock-down of PRMT5 or pharmacological inhibition of PRMT5 suppressed the induction of NED and increased the sensitivity to chemotherapy.Conclusion: Taken together, our results suggest that targeting PRMT5 may be explored as a chemosensitization approach by inhibiting chemotherapy-induced NED.
第一作者单位：[1]Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy, West Lafayette, Indiana, USA[2]Department of Gastroenterology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China[*1]Department of Gastroenterology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
通讯作者：
通讯机构：[1]Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy, West Lafayette, Indiana, USA[2]Department of Gastroenterology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China[*1]Department of Gastroenterology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.[*2]Department of Medicinal Chemistry and Molecular Pharmacology Purdue University College of Pharmacy 201 South University St., West Lafayette, IN 47907, USA.
