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@ARTICLE{Shukla:127516,
author = {K. Shukla$^*$ and A. K. Sharma$^*$ and A. Ward$^*$ and R.
Will$^*$ and T. Hielscher$^*$ and A. Balwierz$^*$ and C.
Breunig$^*$ and E. Münstermann$^*$ and R. König$^*$ and I.
Keklikoglou$^*$ and S. Wiemann$^*$},
title = {{M}icro{RNA}-30c-2-3p negatively regulates {NF}-κ{B}
signaling and cell cycle progression through downregulation
of {TRADD} and {CCNE}1 in breast cancer.},
journal = {Molecular oncology},
volume = {9},
number = {6},
issn = {1574-7891},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2017-03539},
pages = {1106 - 1119},
year = {2015},
abstract = {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.},
keywords = {CCNE1 protein, human (NLM Chemicals) / Cyclin E (NLM
Chemicals) / MIRN30 microRNA, human (NLM Chemicals) /
MicroRNAs (NLM Chemicals) / NF-kappa B (NLM Chemicals) /
Oncogene Proteins (NLM Chemicals) / RNA, Neoplasm (NLM
Chemicals) / TNF Receptor-Associated Death Domain Protein
(NLM Chemicals)},
cin = {B050 / B080 / W110 / C060},
ddc = {610},
cid = {I:(DE-He78)B050-20160331 / I:(DE-He78)B080-20160331 /
I:(DE-He78)W110-20160331 / I:(DE-He78)C060-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25732226},
pmc = {pmc:PMC5528752},
doi = {10.1016/j.molonc.2015.01.008},
url = {https://inrepo02.dkfz.de/record/127516},
}