Chaoyu Wang , Ping Yuan , Dai Yang , Boke Liu , Juyong Liang
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引用次数: 0
Abstract
Background
The circadian rhythm plays a crucial role in thyroid cancer progression. DNA damage repair (DDR) pathways are closely associated with the sensitivity to cisplatin. However, the role of circadian rhythm genes on cisplatin resistance in thyroid cancer remains undefined.
Methods
Panels of molecular screening were achieved by signaling antibody array. Molecular expressions were established via western blotting and polymerase chain reaction (PCR). Multiple assays (Cell Counting Kit-8, colony formation, Transwell) were used to assess cellular dynamics. The xenograft tumor model was employed for in vivo therapeutic evaluation.
Results
BCPAP and KTC-1 cells were more resistant to cisplatin than other thyroid cancer cell lines, and DDR pathway activation was detected upon cisplatin treatment in BCPAP and KTC-1. The target that affects cisplatin efficacy was screened among circadian rhythm genes, and found that TIMELESS expression was correlated with the sensitivity to cisplatin and malignant signatures of thyroid cancer. TIMELESS knockdown impaired the DDR pathway activation, and significantly enhanced the efficacy of cisplatin treatment in vitro and in vivo.
Conclusions
The newly identified signaling involving circadian rhythm genes and DDR pathways provided mechanistic insights into the cisplatin sensitization strategy in thyroid cancer. Therefore, TIMELESS may be a promising target in thyroid cancer therapeutics.
期刊介绍:
Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.