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Falkenberg, N. ; Anastasov, N. ; Schaub, A. ; Radulovic, V. ; Schmitt, M.* ; Magdolen, V.* ; Aubele, M.

Secreted uPAR isoform 2 (uPAR7b) is a novel direct target of miR-221.

Oncotarget 6, 8103-8114 (2015)
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miR-221/-222 and components of the urokinase-type plasminogen activator system (uPAS) are associated with metastasis and poor prognosis in breast cancer, including the triple-negative subtype (TNBC). Modification of components of uPAS and involved miRNAs may contribute to targeted therapy for breast cancer patients. miR-221-/-222-overexpressing or miR-221-depleted cells were employed for qRT-PCR and Western blots to show associations of uPAR with miR-221/-222. To substantiate direct targeting of miR-221/-222 within 3' UTR of the uPAR isoform 2, in silico analysesand in vitro assays were conducted. Significant associations between miR-221 and uPAR isoform 2 expressions were observed at the mRNA and protein levels in breast cancer cells representing TNBC. For the first time, the uPAR isoform 2 was demonstrated as direct target for miR-221/-222. Inhibition of miR-221 reduced uPAR protein expression and expression of the tumor cell invasion markers vimentin and RHOC. These results demonstrate a direct and positive regulation of the secreted uPAR isoform 2 by miR-221, increasing its protein expression, a prerequisite for malignancy, while the other uPAR isoforms (1, 3 and 4) are indirectly regulated through miR-10b and miR-221/-222. By targeting uPAR isoforms and/or miRNA-221/-222, the diagnosis and therapy of breast cancer, in particular in TNBC, could be significantly improved.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Plaur ; Mir-222 ; Microrna ; Soluble ; Therapy; Urokinase Plasminogen-activator; Messenger-rna Stability; Breast-cancer Cells; Tamoxifen Resistance; Receptor; Expression; Micrornas; Promotes; Invasion; Stabilization
ISSN (print) / ISBN 1949-2553
e-ISSN 1949-2553
Journal OncoTarget
Quellenangaben Volume: 6, Issue: 10, Pages: 8103-8114 Article Number: , Supplement: ,
Publisher Impact Journals LLC
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Pathology (PATH)
Institute of Radiation Biology (ISB)