001     127516
005     20240228140933.0
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
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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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)
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|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
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700 1 _ |a Ward, Aoife
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700 1 _ |a Will, Rainer
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700 1 _ |a Hielscher, Thomas
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700 1 _ |a Balwierz, Aleksandra
|0 P:(DE-HGF)0
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700 1 _ |a Breunig, Christian
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700 1 _ |a Münstermann, Ewald
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700 1 _ |a König, Rainer
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700 1 _ |a Keklikoglou, Ioanna
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700 1 _ |a Wiemann, Stefan
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773 _ _ |a 10.1016/j.molonc.2015.01.008
|g Vol. 9, no. 6, p. 1106 - 1119
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|p 1106 - 1119
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