Evidence map›Paper›PMID 25732226›Full record

ArticleMolecular oncology2015

MicroRNA-30c-2-3p negatively regulates NF-κB signaling and cell cycle progression through downregulation of TRADD and CCNE1 in breast cancer.

Kirti Shukla, Ashwini Kumar Sharma, Aoife Ward, Rainer Will, Thomas Hielscher, Aleksandra Balwierz, Christian Breunig, Ewald Münstermann, Rainer König, Ioanna Keklikoglou and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Kirti ShuklaDivision of Molecular Genome Analysis, DKFZ, 69120 Heidelberg, Germany. Electronic address: kirti.iitr@gmail.com.
Ashwini Kumar SharmaDivision of Theoretical Bioinformatics, DKFZ, 69120 Heidelberg, Germany.
Aoife WardDivision of Molecular Genome Analysis, DKFZ, 69120 Heidelberg, Germany.
Rainer WillGenomics & Proteomics Core Facility, DKFZ, 69120 Heidelberg, Germany.
Thomas HielscherDivision of Biostatistics, DKFZ, 69120 Heidelberg, Germany.
Aleksandra BalwierzDivision of Molecular Genome Analysis, DKFZ, 69120 Heidelberg, Germany.
Christian BreunigDivision of Molecular Genome Analysis, DKFZ, 69120 Heidelberg, Germany.
Ewald MünstermannDivision of Molecular Genome Analysis, DKFZ, 69120 Heidelberg, Germany.
Rainer KönigIntegrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany; Network Modeling, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute Jena, Beutenbergstrasse 11a, 07745 Jena, Germany; Division of Theoretical Bioinformatics, DKFZ, 69120 Heidelberg, Germany.
Ioanna KeklikoglouDivision of Molecular Genome Analysis, DKFZ, 69120 Heidelberg, Germany.
Stefan WiemannDivision of Molecular Genome Analysis, DKFZ, 69120 Heidelberg, Germany. Electronic address: s.wiemann@dkfz.de.
Heidelberg University · DEDKFZ-ZMBH Alliance · DEJena University Hospital · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Cell CycleSignal TransductionBreast NeoplasmsCell Line, TumorCyclin EFemaleHumansMicroRNAsNF-kappa BOncogene ProteinsRNA, NeoplasmTNF Receptor-Associated Death Domain ProteinCCNE1 protein, humanCyclin EMicroRNAsMIRN30b microRNA, humanNF-kappa BOncogene ProteinsRNA, NeoplasmTNF Receptor-Associated Death Domain ProteinBreast cancerCell cycle progressionMicroRNANF-κB signaling

Identifiers

PMID25732226
PMCPMC5528752
OpenAlexW1991646209

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.