Radioresistance has remained the major cause of local relapse and distant metastasis in lung cancer. However, the underlying molecular mechanisms remain poorly defined. In this study, we report that Cyclin K is frequently overexpressed and correlated with poor prognosis in lung cancer patients. Functionally, we demonstrate that Cyclin K depletion exhibits reduced proliferation, defective G2/M checkpoint and enhanced radiosensitivity in lung cancer. Mechanistically, we reveal that Cyclin K interacts with and stimulates the transcriptional activity of -catenin, thereby upregulating the expression of Cyclin D1. More importantly, we show that Cyclin D1 is the major effector which mediates the biological functions of Cyclin K in lung cancer. Collectively, our findings suggest that Cyclin K positively modulates -catenin/Cyclin D1 axis to promote tumorigenesis and radioresistance in lung cancer, indicating Cyclin K may be a novel attractive biomarker for lung cancer radiotherapy. SOURCE: Yao Guojun (m201775548@hust.edu.cn) -  Hua Zhong University of science and technology

Pluto Bioinformatics

GSE143147: Cyclin K interacts with -catenin to induce Cyclin D1 expression and facilitate tumorigenesis and radioresistance in lung cancer