Cyclin Y interacts with Chk1 to activate RRM2/STAT3 signaling and promotes radioresistance in non-small cell lung cancer.

Abstract

Radioresistance is one of the main reasons for the recurrence and metastasis of non-small cell lung cancer. Cyclin Y has been implicated in various cellular processes such as cell growth, proliferation, autophagy, and tumor progression. However, the function and regulatory mechanism of Cyclin Y in lung cancer radioresistance remain poorly understood. In this study, we find that Cyclin Y is overexpressed in non-small cell lung cancer and correlates with poor prognosis. Furthermore, knockdown of Cyclin Y results in inhibited cell growth and proliferation, increases DNA damage, impairs DNA damage repair, and enhances radiosensitivity in vitro and in vivo. Mechanistically, we uncover that Cyclin Y interacts with Chk1 and positively regulate both the mRNA and protein levels of RRM2, resulting in increased STAT3 phosphorylation. Rescue experiments confirm that the effects of Cyclin Y on lung cancer are mediated partially by RRM2. Collectively, we reveal for the first time that Cyclin Y promotes lung cancer radioresistance by binding to Chk1 to activate RRM2/STAT3 signaling, indicating that targeting Cyclin Y may be a promising strategy for enhancing the efficacy of radiotherapy in the treatment of non-small cell lung cancer.