The Modulatory Role of MicroRNA-873 in the Progression of KRAS-Driven Cancers
| العنوان: | The Modulatory Role of MicroRNA-873 in the Progression of KRAS-Driven Cancers |
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| المؤلفون: | Bulent Ozpolat, Tamer M. Abdelghany, Stephen T. C. Wong, Kubra Karagoz, Nermin Kahraman, Recep Bayraktar, Michael L. Gatza, Nashwa N. Kabil, Ahmed Ashour, Hamada Ahmed Mokhlis, Abdel Aziz H. Abdel Aziz, Jianting Sheng, Gabriel Lopez-Berestein, Ayşe Caner, Cristian Rodriguez-Aguayo, Erika P. Zambalde, Pinar Kanlikilicer, George A. Calin |
| المصدر: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 14, Iss, Pp 301-317 (2019) |
| بيانات النشر: | American Society of Gene & Cell Therapy, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, liposomes, endocrine system diseases, proliferation, non-coding RNA, pancreatic cancer, Biology, miR-873, medicine.disease_cause, Article, 03 medical and health sciences, gene silencing, 0302 clinical medicine, breast cancer, oncogene, Pancreatic cancer, Drug Discovery, microRNA, medicine, KRAS, Gene silencing, PI3K/AKT/mTOR pathway, Triple-negative breast cancer, therapy, Oncogene, lcsh:RM1-950, medicine.disease, invasion, ncRNA, digestive system diseases, tumorigenesis, lcsh:Therapeutics. Pharmacology, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, triple-negative breast cancer, Molecular Medicine, nanoparticles, Carcinogenesis, gene regulation |
| الوصف: | KRAS is one of the most frequently mutated proto-oncogenes in pancreatic ductal adenocarcinoma (PDAC) and aberrantly activated in triple-negative breast cancer (TNBC). A profound role of microRNAs (miRNAs) in the pathogenesis of human cancer is being uncovered, including in cancer therapy. Using in silico prediction algorithms, we identified miR-873 as a potential regulator of KRAS, and we investigated its role in PDAC and TNBC. We found that reduced miR-873 expression is associated with shorter patient survival in both cancers. miR-873 expression is significantly repressed in PDAC and TNBC cell lines and inversely correlated with KRAS levels. We demonstrate that miR-873 directly bound to the 3′ UTR of KRAS mRNA and suppressed its expression. Notably, restoring miR-873 expression induced apoptosis; recapitulated the effects of KRAS inhibition on cell proliferation, colony formation, and invasion; and suppressed the activity of ERK and PI3K/AKT, while overexpression of KRAS rescued the effects mediated by miR-873. Moreover, in vivo delivery of miR-873 nanoparticles inhibited KRAS expression and tumor growth in PDAC and TNBC tumor models. In conclusion, we provide the first evidence that miR-873 acts as a tumor suppressor by targeting KRAS and that miR-873-based gene therapy may be a therapeutic strategy in PDAC and TNBC. Keywords: KRAS, oncogene, non-coding RNA, microRNA, ncRNA, miR-873, proliferation, invasion, gene regulation, tumorigenesis, gene silencing, therapy, nanoparticles, pancreatic cancer, liposomes, breast cancer, triple-negative breast cancer |
| اللغة: | English |
| تدمد: | 2162-2531 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8b64782fa7bf17ef4c47bf7f7ebe8fa9Test http://europepmc.org/articles/PMC6348737Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8b64782fa7bf17ef4c47bf7f7ebe8fa9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21622531 |
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