Home > Publications database > MicroRNA-30c-2-3p negatively regulates NF-κB signaling and cell cycle progression through downregulation of TRADD and CCNE1 in breast cancer. > print |
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024 | 7 | _ | |a 10.1016/j.molonc.2015.01.008 |2 doi |
024 | 7 | _ | |a pmid:25732226 |2 pmid |
024 | 7 | _ | |a pmc:PMC5528752 |2 pmc |
024 | 7 | _ | |a 1574-7891 |2 ISSN |
024 | 7 | _ | |a 1878-0261 |2 ISSN |
037 | _ | _ | |a DKFZ-2017-03539 |
041 | _ | _ | |a eng |
082 | _ | _ | |a 610 |
100 | 1 | _ | |a Shukla, Kirti |0 P:(DE-HGF)0 |b 0 |e First author |
245 | _ | _ | |a MicroRNA-30c-2-3p negatively regulates NF-κB signaling and cell cycle progression through downregulation of TRADD and CCNE1 in breast cancer. |
260 | _ | _ | |a Amsterdam [u.a.] |c 2015 |b Elsevier |
336 | 7 | _ | |a article |2 DRIVER |
336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1521640183_922 |2 PUB:(DE-HGF) |
336 | 7 | _ | |a ARTICLE |2 BibTeX |
336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
520 | _ | _ | |a Nuclear Factor kappa B (NF-κB) signaling is frequently deregulated in a variety of cancers and is constitutively active in estrogen receptor negative (ER-) breast cancer subtypes. These molecular subtypes of breast cancer are associated with poor overall survival. We focused on mechanisms of NF-κB regulation by microRNAs (miRNAs), which regulate eukaryotic gene expression at the post-transcriptional level. In a previous genome-wide miRNA screen, we had identified miR-30c-2-3p as one of the strongest negative regulators of NF-κB signaling. Here we have uncovered the underlying molecular mechanisms and its consequences in breast cancer. In vitro results show that miR-30c-2-3p directly targets both TNFRSF1A-associated via death domain (TRADD), an adaptor protein of the TNFR/NF-κB signaling pathway, and the cell cycle protein Cyclin E1 (CCNE1). Ectopic expression of miR-30c-2-3p downregulated essential cytokines IL8, IL6, CXCL1, and reduced cell proliferation as well as invasion in MDA-MB-231 breast cancer cells. RNA interference (RNAi) induced silencing of TRADD phenocopied the effects on invasion and cytokine expression caused by miR-30c-2-3p, while inhibition of CCNE1 phenocopied the effects on cell proliferation. We further confirmed the tumor suppressive role of this miRNA using a dataset of 781 breast tumors, where higher expression was associated with better survival in breast cancer patients. In summary we have elucidated the mechanism by which miR-30c-2-3p negatively regulates NF-κB signaling and cell cycle progression in breast cancer. |
536 | _ | _ | |a 312 - Functional and structural genomics (POF3-312) |0 G:(DE-HGF)POF3-312 |c POF3-312 |f POF III |x 0 |
588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
650 | _ | 7 | |a CCNE1 protein, human |2 NLM Chemicals |
650 | _ | 7 | |a Cyclin E |2 NLM Chemicals |
650 | _ | 7 | |a MIRN30 microRNA, human |2 NLM Chemicals |
650 | _ | 7 | |a MicroRNAs |2 NLM Chemicals |
650 | _ | 7 | |a NF-kappa B |2 NLM Chemicals |
650 | _ | 7 | |a Oncogene Proteins |2 NLM Chemicals |
650 | _ | 7 | |a RNA, Neoplasm |2 NLM Chemicals |
650 | _ | 7 | |a TNF Receptor-Associated Death Domain Protein |2 NLM Chemicals |
700 | 1 | _ | |a Sharma, Ashwini Kumar |0 P:(DE-He78)ef6b064b6d3463cee768ed2e261c10cd |b 1 |u dkfz |
700 | 1 | _ | |a Ward, Aoife |0 P:(DE-HGF)0 |b 2 |
700 | 1 | _ | |a Will, Rainer |0 P:(DE-He78)18218139eec55d83cf82679934e5cd75 |b 3 |u dkfz |
700 | 1 | _ | |a Hielscher, Thomas |0 P:(DE-He78)743a4a82daab55306a2c88b9f6bf8c2f |b 4 |u dkfz |
700 | 1 | _ | |a Balwierz, Aleksandra |0 P:(DE-HGF)0 |b 5 |
700 | 1 | _ | |a Breunig, Christian |0 P:(DE-He78)cfaf278e8f522c72644cee2a753d2845 |b 6 |u dkfz |
700 | 1 | _ | |a Münstermann, Ewald |0 P:(DE-He78)610dc3a15bda751de4d4c52373b2620f |b 7 |u dkfz |
700 | 1 | _ | |a König, Rainer |0 P:(DE-He78)4291b9a1fa95bfd7a810372e2d629c32 |b 8 |u dkfz |
700 | 1 | _ | |a Keklikoglou, Ioanna |0 P:(DE-HGF)0 |b 9 |
700 | 1 | _ | |a Wiemann, Stefan |0 P:(DE-He78)f6bebe05e7a748d3cbf9f59659567d52 |b 10 |e Last author |u dkfz |
773 | _ | _ | |a 10.1016/j.molonc.2015.01.008 |g Vol. 9, no. 6, p. 1106 - 1119 |0 PERI:(DE-600)2322586-5 |n 6 |p 1106 - 1119 |t Molecular oncology |v 9 |y 2015 |x 1574-7891 |
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