CRY1Regulates Chemoresistance in Association WithNANOGby Inhibiting Apoptosisvia STAT3Pathway in Patients With Cervical Cancer

GWAN HEE HAN & STEPHEN M. HEWITT et al.

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. 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. 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. 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.
Authors
GWAN HEE HAN, JULIE KIM, HEE YUN, HANBYOUL CHO, JOON-YONG CHUNG, JAE-HOON KIM, STEPHEN M. HEWITT