CRY1 Regulates Chemoresistance in Association with NANOG by Inhibiting Apoptosis via STAT3 Pathway in Patients with Cervical Cancer

Gwan Hee Han, Julie Kim, Hee Yun, Hanbyoul Cho, Joon Yong Chung, Jae Hoon Kim, Stephen M. Hewitt

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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 overexpression serves as a strong predictive biomarker for prognosis and chemoradiation response, and may be a new therapeutic target in patients with cervical cancer.

Original languageEnglish
Pages (from-to)699-713
Number of pages15
JournalCancer Genomics and Proteomics
Issue number6
Publication statusPublished - 2021 Nov

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MIST) (NRF-2020R1A2C2004782). This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (NRF-2017M3A9B8 069610). This study was also supported by a faculty research grant of Yonsei University College of Medicine (No. 6-2020-0226).

Funding Information:
Patients and tumour samples. A total of 188 cervical cancer specimens, 318 high-grade cervical intraepithelial neoplasia (CIN) specimens, 102 low-grade CIN, and 270 normal non-adjacent cervical epithelial tissues were collected from patients who underwent either radical hysterectomy or conisation at the Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine between March 1996 and March 2010. Additional formalin-fixed, paraffin-embedded (FFPE) blocks were provided by the Korea Gynecologic Cancer Bank under the Bio & Medical Technology Development Program of the Ministry of the National Research Foundation (NRF) funded by the Korean government (MIST) (NRF-2017M3A9B8069610). After performing a pathology review of all the tumour specimens, adequate specimens were included in the present study. The clinicopathological characteristics, including age, survival time, survival status, tumour size, grade, cell types, presence of lymph node (LN) metastasis or lymphovascular space invasion, and response to CCRT were obtained from the pathology and medical reports. Cervical cancer staging was performed according to the International Federation of Gynaecology and Obstetrics (FIGO) staging system, and tumour grade was determined as per the World Health Organisation grading. Patients who were eligible for surgical resection underwent type 3 radical hysterectomy with pelvic LN dissection; CCRT was performed after the surgery in patients with a risk of relapse, positive LNs, parametrial invasion, or positive resection margins. Response to therapy was evaluated according to the response evaluation criteria in solid tumours (RECIST; version 1.1) using either computed tomography or magnetic resonance imaging. The present study was approved by the Institutional Review Board (IRB) of Gangnam Severance Hospital (IRB no. 3-2020-0377).

Publisher Copyright:
© 2021 International Institute of Anticancer Research. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cancer Research


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