dc.contributor.author | Raza, Umar | |
dc.contributor.author | Saatci, Özge | |
dc.contributor.author | Uhlmann, Stefan | |
dc.contributor.author | Ansari, Suhail A | |
dc.contributor.author | Eyüpoğlu, Erol | |
dc.contributor.author | Yurdusev, Emre | |
dc.contributor.author | Mutlu, Merve | |
dc.contributor.author | Ersan, Pelin Gülizar | |
dc.contributor.author | Altundağ, Mustafa Kadri | |
dc.contributor.author | Zhang, Jitao David | |
dc.contributor.author | Doğan, Hayriye Tatlı | |
dc.contributor.author | Güler, Gülnur | |
dc.contributor.author | Şahin, Özgür | |
dc.date.accessioned | 2019-12-10T11:20:53Z | |
dc.date.available | 2019-12-10T11:20:53Z | |
dc.date.issued | 2016 | |
dc.identifier.issn | 1949-2553 | |
dc.identifier.uri | https://doi.org/10.18632/oncotarget.10489 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226553/ | |
dc.identifier.uri | http://hdl.handle.net/11655/15398 | |
dc.description.abstract | Tumor cells develop drug resistance which leads to recurrence and distant metastasis. MicroRNAs are key regulators of tumor pathogenesis; however, little is known whether they can sensitize cells and block metastasis simultaneously. Here, we report miR-644a as a novel inhibitor of both cell survival and EMT whereby acting as pleiotropic therapy-sensitizer in breast cancer. We showed that both miR-644a expression and its gene signature are associated with tumor progression and distant metastasis-free survival. Mechanistically, miR-644a directly targets the transcriptional co-repressor C-Terminal Binding Protein 1 (CTBP1) whose knock-outs by the CRISPR-Cas9 system inhibit tumor growth, metastasis, and drug resistance, mimicking the phenotypes induced by miR-644a. Furthermore, downregulation of CTBP1 by miR-644a upregulates wild type- or mutant-p53 which acts as a ‘molecular switch’ between G1-arrest and apoptosis by inducing cyclin-dependent kinase inhibitor 1 (p21, CDKN1A, CIP1) or pro-apoptotic phorbol-12-myristate-13-acetate-induced protein 1 (Noxa, PMAIP1), respectively. Interestingly, an increase in mutant-p53 by either overexpression of miR-644a or downregulation of CTBP1 was enough to shift this balance in favor of apoptosis through upregulation of Noxa. Notably, p53-mutant patients, but not p53-wild type ones, with high CTBP1 have a shorter survival suggesting that CTBP1 could be a potential prognostic factor for breast cancer patients with p53 mutations. Overall, re-activation of the miR-644a/CTBP1/p53 axis may represent a new strategy for overcoming both therapy resistance and metastasis. | |
dc.relation.isversionof | 10.18632/oncotarget.10489 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.title | The Mir-644A/Ctbp1/P53 Axis Suppresses Drug Resistance By Simultaneous Inhibition Of Cell Survival And Epithelial-Mesenchymal Transition In Breast Cancer | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:eu-repo/semantics/publishedVersion | |
dc.relation.journal | Oncotarget | |
dc.contributor.department | İç Hastalıkları | |
dc.identifier.volume | 7 | |
dc.identifier.issue | 31 | |
dc.identifier.startpage | 49859 | |
dc.identifier.endpage | 49877 | |
dc.description.index | PubMed | |
dc.description.index | WoS | |
dc.description.index | Scopus | |