Gwan Hee Han1,2, Julie Kim3, Hee Yun4, Hanbyoul Cho5,6,7, Joon-Yong Chung7, Jae-Hoon Kim8,6, Stephen M Hewitt7. 1. Department of Obstetrics and Gynecology, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea. 2. Yonsei University Graduate School, Seoul, Republic of Korea. 3. Weill Cornell Medical College, New York, NY, U.S.A. 4. Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 5. Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea; hanbyoul@yuhs.ac. 6. Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea. 7. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, U.S.A. 8. Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea.
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. Copyright
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. Copyright
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