Cyclin-dependent kinase 8(CDK8) induced ubiquitin specific peptidase 7(USP7) expression to regulate MRN complex and facilitates DNA damage repair in lung cancer

CDK8 plays a critical role in the regulation of various functions in the cell process, including DNA damage and repair. However, the underlying mechanisms remain elusive. In this study, we found that CDK8 was frequently overexpressed, and high level predicted poor prognosis in lung cancer patients. Furthermore, we observed that downregulation of CDK8 in NSCLC cells exhibited enhanced irradiation-induced and cisplatin-induced DNA damage. Mechanically, CDK8 promoted the transcription activity of USP7, and then regulated the phosphorylation of MRN complex after irradiation. Our results figured out a brand-new CDK8/USP7/MRN complex axis as well as its critical regulation of irradiation-induced and cisplatin-induced DNA damage in NSCLC, which might be a promising new strategy for radiotherapy and chemotherapy resistance.