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Kleemann, M.* ; Schneider, H.* ; Unger, K. ; Sander, P.* ; Schneider, E.M.* ; Fischer-Posovszky, P.* ; Handrick, R.* ; Otte, K.*

MiR-744-5p inducing cell death by directly targeting HNRNPC and NFIX in ovarian cancer cells.

Sci. Rep. 8:9020 (2018)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
MicroRNAs (miRNAs) play an important role in the regulation of gene expression. The binding to target messenger RNAs (mRNAs) results in mRNA cleavage or inhibition of the translational machinery leading to decreased protein levels. Various signalling pathways, including apoptosis are modulated by miRNAs. Here, we investigated the role of miR-744-5p in apoptosis signalling in ovarian cancer cell lines. MiR-744-5p expression was reduced in the cancer cell lines independent of the host gene MAP2K4. Overexpression of miR-744-5p activated the intrinsic apoptotic pathway in SKOV3, OVCAR3 and Cisplatin resistant (A2780-cis) and non-resistant A2780 cells leading to cell death. Notably, miR-744-5p overexpression together with Carboplatin treatment led to at least additive pro-apoptotic effects. Investigation of the apoptotic signalling pathways mediated by miR-744-5p revealed that its elevated expression directly downregulated mRNA and protein expression of nuclear factor I X (NFIX) and heterogeneous nuclear ribonucleoprotein C (HNRNPC). HNRNPC caused diminished miR-21 expression and AKT phosphorylation, while NFIX decreased Bcl2 levels, leading to the detected pro-apoptotic effects. Finally, Kaplan-Meier-Plots showed a prolonged median disease-free survival in ovarian serous cystadenocarcinoma patients with high miR-744 expression.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords TUMOR-SUPPRESSOR; INDUCED APOPTOSIS; GENE-EXPRESSION; CARCINOMA CELLS; MIRNA; PATHWAY; DNA; GLIOBLASTOMA; PROGRESSION; BIOGENESIS
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Quellenangaben Volume: 8, Issue: 1, Pages: , Article Number: 9020 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed