REV1 promotes lung tumorigenesis by activating the Rad18/SERTAD2 axis

REV1 is the central member of the family of TLS polymerases, which participate in various DNA damage repair and tolerance pathways, including translesion DNA synthesis, 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. Overall design: A549 cells transfected with Scrambled or SiRNAs targeting REV1 for 48 hours were analyzed by RNA-seq.