Department of Obstetrics and Gynecology, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.
Yonsei University Graduate School, Seoul, Republic of Korea.
Cancer Genomics Proteomics. 2021 Nov-Dec;18(6):699-713. doi: 10.21873/cgp.20291.
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.
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.
背景/目的:隐色素 1(CRY1)是核心生物钟基因,调节昼夜节律和致癌作用。本研究旨在探讨 CRY1 及其与干细胞转录因子 NANOG 之间的关系在宫颈癌中的作用。
采用组织微阵列免疫组化检测宫颈癌组织中 CRY1 和 NANOG 的表达,并在宫颈癌细胞系中评估其功能作用。
CRY1 或 NANOG 在宫颈癌组织中呈显著过表达。值得注意的是,CRY1 和 NANOG 的联合过表达与显著不良的 OS 和 DFS 相关,并且比每种单一蛋白具有更强的预测放化疗反应的价值。此外,siCRY1 可诱导宫颈癌细胞系凋亡、降低 NANOG 表达、抑制 STAT3 信号通路、激活 p53 信号通路。
CRY1 和 NANOG 的过表达可作为预后和放化疗反应的强预测生物标志物,可能成为宫颈癌患者的新治疗靶点。