dc.contributor.author
Wotschofsky, Zofia
dc.contributor.author
Gummlich, Linda
dc.contributor.author
Liep, Julia
dc.contributor.author
Stephan, Carsten
dc.contributor.author
Kilic, Ergin
dc.contributor.author
Jung, Klaus
dc.contributor.author
Billaud, Jean-Noel
dc.contributor.author
Meyer, Hellmuth-Alexander
dc.date.accessioned
2018-06-08T07:16:53Z
dc.date.available
2016-03-18T12:55:29.913Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/17571
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-21455
dc.description.abstract
Background MicroRNAs (miRNAs) regulate gene expression by interfering
translation or stability of target transcripts. This interplay between miRNA
and their mRNA has been proposed as an important process in cancer development
and progression. We have investigated molecular networks impacted by predicted
mRNA targets of differentially expressed miRNAs in patients with clear cell
renal cell carcinoma (ccRCC) diagnosed with or without metastasis. Material
and Methods miRNA and mRNA microarray expression profiles derived from primary
ccRCC from patients with (16 samples) or without diagnosed metastasis (22
samples) were used to identify anti-correlated miRNA-mRNA interaction in
ccRCC. For this purpose, Ingenuity pathway analysis microRNA Target Filter,
which enables prioritization of experimentally validated and predicted mRNA
targets was used. By applying an expression pairing tool, the analysis was
focused on targets exhibiting altered expression in our analysis, finding
miRNAs and their target genes with opposite or same expression. The resulting
identified interactions were revalidated by RT-qPCR in another cohort of ccRCC
patients. A selection of the predicted miRNA-mRNA interactions was tested by
functional analyses using miRNA knockdown and overexpression experiments in
renal cancer cell lines. Results Among the significantly differentially
expressed miRNAs, we have identified three miRNAs (miR-146a-5p, miR-128a-3p,
and miR-17-5p) that were upregulated in primary tumors from patients without
metastasis and downregulated in primary tumors from patients with metastasis.
We have further identified mRNA targets, which expression were inversely
correlated to these 3 miRNAs, and have been previously experimentally
demonstrated in cancer setting in humans. Specifically, we showed that
CXCL8/IL8, UHRF1, MCM10, and CDKN3 were downregulated and targeted by miR-
146a-5p. The interaction between miR-146a-5p and their targets CXCL8 and UHRF1
was validated in cell culture experiments. Conclusions We identified novel
target genes of dysregulated miRNAs, which are involved in the transition from
primary RCC without metastases into tumors generating distant metastasis.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Integrated microRNA and mRNA Signature Associated with the Transition from the
Locally Confined to the Metastasized Clear Cell Renal Cell Carcinoma
Exemplified by miR-146-5p
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
PLoS ONE. - 11 (2016), 2, Artikel Nr. e0148746
dcterms.bibliographicCitation.doi
10.1371/journal.pone.0148746
dcterms.bibliographicCitation.url
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148746
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000024194
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000006142
dcterms.accessRights.openaire
open access