Targeting HMGB3/hTERT axis for radioresistance in cervical cancer
| العنوان: | Targeting HMGB3/hTERT axis for radioresistance in cervical cancer |
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| المؤلفون: | Anshi Zhao, Liru He, Kun Zou, Wuguo Deng, Lijuan Zou, Xiaoyuan Tian, Wendan Yu, Zongjuan Li, Silei Sui, Ruonan Wang, Wei Guo, Yijun Hua, Yang Zhang |
| المصدر: | Journal of Experimental & Clinical Cancer Research : CR Journal of Experimental & Clinical Cancer Research, Vol 39, Iss 1, Pp 1-17 (2020) |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, medicine.medical_treatment, Mice, Nude, Uterine Cervical Neoplasms, Transfection, lcsh:RC254-282, Radiation Tolerance, Mice, 03 medical and health sciences, 0302 clinical medicine, In vivo, Cell Line, Tumor, HMGB3 Protein, Radioresistance, medicine, Animals, Humans, Telomerase reverse transcriptase, Cervical cancer, Gene knockdown, HMGB3, Cell growth, business.industry, Research, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Radiation therapy, 030104 developmental biology, Oncology, Apoptosis, 030220 oncology & carcinogenesis, Cancer research, Female, hTERT, business, Signal Transduction |
| الوصف: | Background Radiotherapy is regarded as a milestone for the cure of cervical cancer. However, clinical outcome heavily be hindered by radioresistance. So, exploring the underlying mechanism of radioresistance, and find potential target, well deserve fully emphasis. Methods In this study, we developed two novel radiation resistance cervical cancer cell lines, which could mimic clinical radioresistance. In order to find new potential targets, RNA-Seq, database analysis, streptavidin-agarose and LC/MS were used. Pull-down, luciferase and rescue assays were conducted to explore the regulatory mechanisms. To further evaluate the correlation between therapeutic responses and HMGB3/hTERT expression, 172 cervical cancer patients were recruited. Results Knockdown of HMGB3 significantly inhibit the DNA damage repair and induced more γH2AX foci, leading to enhanced chemo- and radio-sensitivity in vitro and in vivo, whereas HMGB3 overexpression has the opposite effects. HMGB3 promotes cell growth and radioresistance by transcriptionally up-regulating hTERT via the specifical binding of HMGB3 at the hTERT promoter region from − 902 to − 321. HMGB3 knockdown-mediated radiosensitization could be reversed by the overexpressed hTERT in both cervical cancer cell lines and xenograft tumor mouse model. Furthermore, clinical data from 172 cervical cancer patients proved that there was a positive correlation between HMGB3 and hTERT expression, and high expression of HMGB3/hTERT predicted poor response to radiotherapy, worse TNM stages and shorter survival time. Conclusion Here, we have identified HMGB3/hTERT signaling axis as a new target for cervical cancer radioresistance. Our results provide new insights into the mechanism of cervical cancer radioresistance and indicate that targeting the HMGB3/hTERT signaling axis may benefit cervical cancer patients. |
| تدمد: | 1756-9966 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1605d94aeaa3d428ef1ac1c367a7572b https://doi.org/10.1186/s13046-020-01737-1 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1605d94aeaa3d428ef1ac1c367a7572b |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 17569966 |
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