<i>CRY1</i>Regulates Chemoresistance in Association With<i>NANOG</i>by Inhibiting Apoptosis<i>via STAT3</i>Pathway in Patients With Cervical Cancer
Gwan Hee Han, Julie Kim, Hee Yun, Hanbyoul Cho, Joon‐Yong Chung, Jae‐Hoon Kim, Stephen M. Hewitt
Abstract
BACKGROUND/AIM: Cryptochrome 1 (CRY1), a core circadian gene, modulates circadian rhythm and carcinogenesis. Here, we investigated the role of CRY1 and its correlation with NANOG, a stem cell transcription factor, in cervical cancer. MATERIALS AND METHODS: Immunohistochemistry with tissue microarray was performed to evaluate CRY1 and NANOG expression in cervical cancer tissues, and their functional roles were assessed in cervical cancer cell lines. RESULTS: CRY1 or NANOG was significantly over-expressed in cervical cancer tissues. Notably, combined over-expression of CRY1 and NANOG was correlated with a significantly poor OS and DFS and showed a stronger predictive value for chemoradiation response than each single protein. Furthermore, siCRY1 induced apoptosis, decreased NANOG expression, suppressed STAT3 signalling, and activated p53 signalling in cervical cancer cell lines. CONCLUSION: CRY1 and NANOG over-expression serves as a strong predictive biomarker for prognosis and chemoradiation response, and may be a new therapeutic target in patients with cervical cancer.