miR-221 Augments TRAIL-Mediated Apoptosis in Prostate Cancer Cells by Inducing Endogenous TRAIL Expression and Targeting the Functional Repressors SOCS3 and PIK3R1

Figure 2

Interaction of TRAIL and interferon signalling in PCa tissue and cells and its modulation by miR-221 expression. (a) DAVID Functional Annotation analysis of Affymetrix microarray data (PC3 cells, pre-miR-221 vs. anti-miR-221 transfections, 48 h p. t.) identified interferon-related cellular functions as being significantly enriched. (b) Significant overexpression of XAF1, TNFSF10, and STAT1 in miR-221 overexpressing PC3 cells within microarray experiments (pre-miR-221 vs- anti-miR-221 and pre-miR-221 vs. pre-miR-Ctr, 48 h p. t.). (c) qRT-PCR confirmed a significant upregulation of TNFSF10, XAF1, and STAT1 expression as well as (d) a significant downregulation of SOCS3 after restoration of miR-221 levels in PC3 cells compared to control (48 h p. t.). Data represent mean + SD from five independent experiments, *; **. (e) Reactome pathway analysis of top 50 genes positively correlated with TNFSF10/TRAIL expression within TCGA dataset (Prostate Adenocarcinoma, PanCancer Atlas). FDR: false discovery rate.

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