The Modulatory Role of MicroRNA-873 in the Progression of KRAS-Driven Cancers
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...
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Elsevier,
2019-03-01T00:00:00Z.
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| 001 | doaj_b75b51d3900244c191dd8e85ccf9ff8e | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Hamada A. Mokhlis |e author |
| 700 | 1 | 0 | |a Recep Bayraktar |e author |
| 700 | 1 | 0 | |a Nashwa N. Kabil |e author |
| 700 | 1 | 0 | |a Ayse Caner |e author |
| 700 | 1 | 0 | |a Nermin Kahraman |e author |
| 700 | 1 | 0 | |a Cristian Rodriguez-Aguayo |e author |
| 700 | 1 | 0 | |a Erika P. Zambalde |e author |
| 700 | 1 | 0 | |a Jianting Sheng |e author |
| 700 | 1 | 0 | |a Kübra Karagoz |e author |
| 700 | 1 | 0 | |a Pinar Kanlikilicer |e author |
| 700 | 1 | 0 | |a Abdel Aziz H. Abdel Aziz |e author |
| 700 | 1 | 0 | |a Tamer M. Abdelghany |e author |
| 700 | 1 | 0 | |a Ahmed A. Ashour |e author |
| 700 | 1 | 0 | |a Stephen Wong |e author |
| 700 | 1 | 0 | |a Michael L. Gatza |e author |
| 700 | 1 | 0 | |a George A. Calin |e author |
| 700 | 1 | 0 | |a Gabriel Lopez-Berestein |e author |
| 700 | 1 | 0 | |a Bulent Ozpolat |e author |
| 245 | 0 | 0 | |a The Modulatory Role of MicroRNA-873 in the Progression of KRAS-Driven Cancers |
| 260 | |b Elsevier, |c 2019-03-01T00:00:00Z. | ||
| 500 | |a 2162-2531 | ||
| 500 | |a 10.1016/j.omtn.2018.11.019 | ||
| 520 | |a 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 | ||
| 546 | |a EN | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Molecular Therapy: Nucleic Acids, Vol 14, Iss , Pp 301-317 (2019) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S2162253118303172 | |
| 787 | 0 | |n https://doaj.org/toc/2162-2531 | |
| 856 | 4 | 1 | |u https://doaj.org/article/b75b51d3900244c191dd8e85ccf9ff8e |z Connect to this object online. |