REV1 promotes lung tumorigenesis by activating the Rad18/SERTAD2 axis

Autor: Yunshang Chen, Xiaohua Jie, Biyuan Xing, Zilong Wu, Xijie Yang, Xinrui Rao, Yingzhuo Xu, Dong Zhou, Xiaorong Dong, Tao Zhang, Kunyu Yang, Zhenyu Li, Gang Wu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cell Death and Disease, Vol 13, Iss 2, Pp 1-11 (2022)
Druh dokumentu: article
ISSN: 2041-4889
DOI: 10.1038/s41419-022-04567-5
Popis: Abstract REV1 is the central member of the family of TLS polymerases, which participate in various DNA damage repair and tolerance pathways and play a significant role in maintaining genomic stability. However, the role of REV1 in tumors is rarely reported. In this study, we found that the expression of REV1 was significantly upregulated in lung cancer tissues compared with matched adjacent tissues and was associated with poor prognosis. Functional experiments demonstrated that REV1 silencing decreased the growth and proliferation capacity of lung cancer cells. Mechanistically, REV1 upregulated the expression of SERTAD2 in a Rad18-dependent manner, thereby promoting lung carcinogenesis. A novel REV1 inhibitor, JH-RE-06, suppressed lung tumorigenesis in vivo and in vitro and was shown to be safe and well tolerated. Our study confirmed that REV1 is a potential diagnostic marker and therapeutic target for lung cancer and that JH-RE-06 may be a safe and efficient therapeutic agent for NSCLC.
Databáze: Directory of Open Access Journals