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@ARTICLE{Ast:142283,
author = {V. Ast and T. Kordass$^*$ and M. Oswald and A. Kolte and D.
Eisel$^*$ and W. Osen$^*$ and S. Eichmüller$^*$ and A.
Berndt and R. König},
title = {{M}i{R}-192, mi{R}-200c and mi{R}-17 are
fibroblast-mediated inhibitors of colorectal cancer
invasion.},
journal = {OncoTarget},
volume = {9},
number = {85},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2019-00066},
pages = {35559-35580},
year = {2018},
note = {Ast V*, Kordass T* (*=eqal contribution)},
abstract = {Colorectal cancer remains a leading cause of cancer-related
death worldwide. A previous transcriptomics based study
characterized molecular subgroups of which the stromal
subgroup was associated with the worst clinical outcome.
Micro-RNAs (miRNAs) are well-known regulators of gene
expression and can follow a non-linear repression mechanism.
We set up a model combining piecewise linear and linear
regression and applied this combined regression model to a
comprehensive colon adenocarcinoma dataset. We identified
miRNAs involved in regulating characteristic gene sets,
particularly extracellular matrix remodeling in the stromal
subgroup. Comparison of expression data from separated
(epithelial) cancer cells and stroma cells or fibroblasts
associate these regulatory interactions with infiltrating
stromal or tumor-associated fibroblasts. MiR-200c, miR-17
and miR-192 were identified as the most promising candidates
regulating genes crucial for extracellular matrix
remodeling. We validated our computational findings by in
vitro assays. Enforced expression of either miR-200c, miR-17
or miR-192 in untransformed human colon fibroblasts
down-regulated $85\%$ of all predicted target genes.
Expressing these miRNAs singly or in combination in human
colon fibroblasts co-cultured with colon cancer cells
considerably reduced cancer cell invasion validating these
miRNAs as cancer cell infiltration suppressors in tumor
associated fibroblasts.},
cin = {G182},
ddc = {610},
cid = {I:(DE-He78)G182-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30473751},
pmc = {pmc:PMC6238973},
doi = {10.18632/oncotarget.26263},
url = {https://inrepo02.dkfz.de/record/142283},
}