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Fig. 5 | Cell Communication and Signaling

Fig. 5

From: miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators

Fig. 5

miR-146a overexpression reduces COX2 and increases drug sensitivity in 3D cultures from BRAF/MEKi-resistant tumors. a Overexpression of miR-146a upon transfection of specific mimic (m-miR-146a) in 3D tumor explants (left) downregulates COX2 expression compared to scrambled-transfected control (S) (right). b Reduced COX2 immunostaining in 3D cultures upon miR-146a forced expression (m-miR-146a) compared to mimic scrambled control (S). c Regulation of PTGS2 and miR-146a target genes (upper panel), and decreased release of CCL2, IL6, IL8 and VEGFA (lower panel) upon treatment with miR-146a mimic (m-miR-146a) and BRAF/MEKi in 3D cultures of resistant tumors in comparison to scrambled-transfected control (S). AU: arbitrary units. d PGE2 release in culture media from 3D tumor explants upon celecoxib treatment. **: p < 0.01 by Student’s unpaired t test. e Effects of treatment with BRAF/MEKi combined with transfection of miR-146a mimic (m-miR-146a) or of scrambled control (S) in resistant tumors: reduction of COX2 and of Ki67 positive cells and increase of cleaved caspase 3 immunostaining. Scale bars: 10 μm

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Cell Communication and Signaling

ISSN: 1478-811X