iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a-FBXL5/BTG3 signaling
| العنوان: | iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a-FBXL5/BTG3 signaling |
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| المؤلفون: | Chun yan Lan, Yin Wang, Peixin Dong, Junming Yue, Ying Xiong, Hidemichi Watari, Ze biao Ma, Min fei Yu, Fei Sun |
| المصدر: | Journal of Experimental & Clinical Cancer Research, Vol 36, Iss 1, Pp 1-10 (2017) Journal of Experimental & Clinical Cancer Research : CR |
| بيانات النشر: | BMC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Uterine Cervical Neoplasms, Cell Cycle Proteins, Mice, 0302 clinical medicine, BTG3, Neoplasm Metastasis, Gene knockdown, Chemistry, Intracellular Signaling Peptides and Proteins, EMT, Ubiquitin-Protein Ligase Complexes, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Oncology, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Female, Chemoresistance, Signal Transduction, medicine.drug, Epithelial-Mesenchymal Transition, lcsh:RC254-282, 03 medical and health sciences, Downregulation and upregulation, In vivo, Cell Line, Tumor, microRNA, medicine, Animals, Humans, Gene silencing, Cell Proliferation, Cisplatin, Cell growth, Research, F-Box Proteins, iASPP, Proteins, Repressor Proteins, MicroRNAs, 030104 developmental biology, Drug Resistance, Neoplasm, Apoptosis, Cancer research, Cervical cancer, FBXL5, HeLa Cells |
| الوصف: | Background Epithelial–mesenchymal transition (EMT) and dysregulated microRNAs (miRNAs) have important roles in driving chemoresistance. We previously reported that iASPP is a key EMT inducer and could increase cisplatin resistance in cervical cancer (CC) cells. Herein, we investigate the downstream mechanisms through which iASPP contributes to EMT and cisplatin resistance in CC. Methods By using a lentiviral system, we investigated the effects of iASPP knockdown on CC cell growth and chemosensitivity of CC cells to cisplatin in vivo. We examined if miR-20a, which was up-regulated following iASPP overexpression, would influence metastatic phenotypes and cisplatin resistance in CC cells, and explored the possible molecular mechanisms involved. Results Knockdown of iASPP suppressed CC cell proliferation and sensitized CC cells to cisplatin in vivo. iASPP promotes miR-20a expression in a p53-dependent manner. Upregulation of miR-20a induced EMT and the recovery of CC cell invasion and cisplatin chemoresistance that was repressed by iASPP knockdown. We identified FBXL5 and BTG3 as two direct miR-20a targets. Silencing of FBXL5 and BTG3 restored cell invasion and cisplatin chemoresistance, which was suppressed by iASPP or miR-20a knockdown. Reduced FBXL5 and BTG3 expression was found in CC samples and associated with poor prognosis in CC patients. Conclusions iASPP promotes EMT and confers cisplatin resistance in CC via miR-20a-FBXL5/BTG3 signaling. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0520-6) contains supplementary material, which is available to authorized users. |
| وصف الملف: | application/vnd.openxmlformats-officedocument.wordprocessingml.document; application/pdf |
| اللغة: | English |
| تدمد: | 1756-9966 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bbb2f26103fd96df154b3bef7be83e56Test http://link.springer.com/article/10.1186/s13046-017-0520-6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bbb2f26103fd96df154b3bef7be83e56 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17569966 |
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