永恒的
顺铂
细胞生长
生物
癌症研究
彗星试验
基因敲除
分子生物学
DNA损伤
细胞凋亡
细胞生物学
DNA
生物化学
遗传学
化疗
神经科学
昼夜节律
作者
Jinhua Zhou,Yinghui Zhang,Xinwei Zou,Lingling Kuai,Li Wang,Juan Wang,Fangrong Shen,Jinghui Hu,Xia Zhang,Ya-Zhen Huang,Youguo Chen
出处
期刊:Human Gene Therapy
[Mary Ann Liebert]
日期:2019-12-24
卷期号:31 (5-6): 385-395
被引量:23
摘要
Timeless is a regulator of molecular clockwork in Drosophila and related to cancer development in mammals. This study aimed to investigate the effect of Timeless on cell proliferation and cisplatin sensitivity in cervical cancer. Timeless expression was determined by bioinformatics analysis, immunohistochemistry, and quantitative polymerase chain reaction (qPCR). Chromatin immunoprecipitation assays and reporter gene assays were applied to determine the transcriptional factor contributing to Timeless upregulation. The effects of Timeless depletion on cell proliferation and cisplatin sensitivity were determined through in vitro and in vivo experiments. Cell apoptosis and senescence were assessed by flow cytometry and β-galactosidase staining. DNA damage and DNA repair pathways were determined by comet assay, immunofluorescent staining, and Western blot analysis. Timeless is aberrantly expressed in ∼52.5% of cervical cancer tissues. E2F1 and E2F4 contribute to the transcriptional activation of Timeless. Timeless depletion inhibits cell proliferation and increases cisplatin sensitivity in vitro and in vivo. Knockdown of Timeless induces cell apoptosis and cell senescence. Mechanically, Timeless silencing leads to DNA damage and impairs the activation of the ATR/CHK1 pathway in response to cisplatin in cervical cancer. Timeless is overexpressed in cervical cancer and regulates cell proliferation and cisplatin sensitivity, presenting an attractive target for cisplatin sensitizer in cervical cancer.
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