Unknown

Dataset Information

0

MiRNA-1246 induces pro-inflammatory responses in mesenchymal stem/stromal cells by regulating PKA and PP2A.


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-?B activity. The pro-inflammatory phenotype of miR-1246 in MSCs was independent of TNF? 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.

SUBMITTER: Bott A 

PROVIDER: S-EPMC5546423 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

miRNA-1246 induces pro-inflammatory responses in mesenchymal stem/stromal cells by regulating PKA and PP2A.

Bott Alexander A   Erdem Nese N   Lerrer Shalom S   Hotz-Wagenblatt Agnes A   Breunig Christian C   Abnaof Khalid K   Wörner Angelika A   Wilhelm Heike H   Münstermann Ewald E   Ben-Baruch Adit A   Wiemann Stefan S  

Oncotarget 20170701 27


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 cel  ...[more]

Similar Datasets

2018-10-06 | E-MTAB-7224 | biostudies-arrayexpress
| S-EPMC4911501 | biostudies-literature
| S-EPMC5535070 | biostudies-literature
| S-EPMC3602067 | biostudies-literature
| S-EPMC5910660 | biostudies-literature
| S-EPMC5390105 | biostudies-literature
| S-EPMC5895792 | biostudies-literature
| S-EPMC7519767 | biostudies-literature
| S-EPMC8257582 | biostudies-literature
| S-EPMC7140705 | biostudies-literature