MiR-532-5p suppresses renal cancer cell proliferation by disrupting the ETS1-mediated positive feedback loop with the KRAS-NAP1L1/P-ERK axis
| العنوان: | MiR-532-5p suppresses renal cancer cell proliferation by disrupting the ETS1-mediated positive feedback loop with the KRAS-NAP1L1/P-ERK axis |
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| المؤلفون: | Dongkui Gong, Saiyang Li, Zhiguo Chen, Junjie Ma, Butang Li, Junhua Zheng, Jin Zhang, Yiran Huang, Chen Xu, Rujian Zhu, Chen Chen, Yonghui Chen, Jiayi Zheng, Wei Xue, Wei Zhai |
| المصدر: | British Journal of Cancer |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cancer Research, NAP1L1, MAP Kinase Signaling System, Down-Regulation, Biology, medicine.disease_cause, Article, Tumour biomarkers, Proto-Oncogene Protein c-ets-1, Proto-Oncogene Proteins p21(ras), Cell growth, Mice, 03 medical and health sciences, 0302 clinical medicine, ETS1, Cell Line, Tumor, microRNA, medicine, Animals, Humans, Phosphorylation, Promoter Regions, Genetic, Carcinoma, Renal Cell, Feedback, Physiological, Gene knockdown, Nucleosome Assembly Protein 1, Oncogene, Prognosis, Survival Analysis, Kidney Neoplasms, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, Oncology, A549 Cells, 030220 oncology & carcinogenesis, miRNAs, Cancer research, KRAS, Chromatin immunoprecipitation, Neoplasm Transplantation |
| الوصف: | Background Despite the fact that miRNAs play pivotal roles in various human malignancies, their molecular mechanisms influencing RCC are poorly understood. Methods The expression of miRNAs from RCC and paired normal renal specimens was analysed by a combined computational and experimental approach using two published datasets and qRT-PCR assays. The functional role of these miRNAs was further identified by overexpression and inhibition assays in vivo and in vitro. Western blots, luciferase assays, and chromatin immunoprecipitation were performed to investigate the potential mechanisms of these miRNAs. Results Bioinformatics analysis and qRT-PCR revealed that miR-532-5p was one of the most heavily downregulated miRNAs. Overexpression of miR-532-5p inhibited RCC cell proliferation, while knockdown of miR-532-5p promoted cell proliferation. Mechanistic analyses indicated that miR-532-5p directly targets KRAS and NAP1L1. Interestingly, ETS1 suppressed the transcription of miR-532-5p by directly binding a special region of its promoter. Moreover, high levels of ETS1, as an oncogene in RCC, were significantly associated with poor survival in a large cohort of RCC specimens. Conclusions Our work presents a road map for the prediction and validation of a miR-532-5p/KRAS-NAP1L1/P-ERK/ETS1 axis feedback loop regulating cell proliferation, which could potentially provide better therapeutic avenues for treating RCC. |
| تدمد: | 1532-1827 0007-0920 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::60907bb8ffeedfc13fc38448a0aa183a https://doi.org/10.1038/s41416-018-0196-5 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....60907bb8ffeedfc13fc38448a0aa183a |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15321827 00070920 |
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