Journal Article

DKFZ-2017-01512

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png miRNA-1246 induces pro-inflammatory responses in mesenchymal stem/stromal cells by regulating PKA and PP2A.

Bott, A. (First author)DKFZ* ; Erdem, N.DKFZ* ; Lerrer, S. ; Hotz-Wagenblatt, A.DKFZ* ; Breunig, C.DKFZ* ; Abnaof, K. A.DKFZ* ; Wörner, A.DKFZ* ; Wilhelm, H.DKFZ* ; Münstermann, E.DKFZ* ; Ben-Baruch, A. ; Wiemann, S. (Last author)DKFZ*

2017
Impact Journals LLC [S.l.]

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Please use a persistent id in citations: doi:10.18632/oncotarget.14915

Abstract: The tumor microenvironment (TME) has an impact on breast cancer progression by creating a pro-inflammatory milieu within the tumor. However, little is known about the roles of miRNAs in cells of the TME during this process. We identified six putative oncomiRs in a breast cancer dataset, all strongly correlating with poor overall patient survival. Out of the six candidates, miR-1246 was upregulated in aggressive breast cancer subtypes and expressed at highest levels in mesenchymal stem/stroma cells (MSCs). Functionally, miR-1246 led to a p65-dependent increase in transcription and release of pro-inflammatory mediators IL-6, CCL2 and CCL5 in MSCs, and increased NF-κB activity. The pro-inflammatory phenotype of miR-1246 in MSCs was independent of TNFα stimulations and mediated by direct targeting of the tumor-suppressors PRKAR1A and PPP2CB. In vitro recapitulation of the TME revealed increased Stat3 phosphorylation in breast epithelial (MCF10A) and cancer cells (SK-BR-3, MCF7, T47D) upon incubation with conditioned medium (CM) of MSCs overexpressing miR-1246. Additionally, this stimulation enhanced proliferation of MCF10A cells, increased migration of MDA-MB-231 cells and induced attraction of THP-1 monocytic cells. Our data shows that miR-1246 acts as both key-enhancer of pro-inflammatory responses in MSCs and putative oncomiR in breast cancer, suggesting its influence on cancer-related inflammation and breast cancer progression.

Note: #DKFZ-MOST-Ca153#

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Contributing Institute(s):

1. B050 Molekulare Genomanalyse (B050)
2. Bioinformatik (HUSAR) (W180)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2017

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Database coverage:
; BIOSIS Previews ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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