Tonic suppression of < i > PCAT29 < /i > by the IL-6 signaling pathway in prostate cancer: Reversal by resveratrol

In this study we focused on the lncRNA, prostate cancer associated transc ript 29 (PCAT29), a putative tumor suppressive gene. Our data show that the expression ofPCAT29 was reduced in prostate cancer tumors compared to paired perinormal prostate tissues. We also observed substantially lower levels ofPCAT29 in DU145 and LNCaP cells compared to normal prostate (RWPE-1) cells. IL-6, a cytokine which is elevated in prostate tumors, reduced the expression ofPCAT29 in both DU145 and LNCaP cells by activating signal transducer and activator of transcription 3 (STAT3). One downstream target of STAT3 is microRNA(miR)-21, inhibition of which enhanced basalPCAT29 expression. In addition, we show that resveratrol is a potent stimulator ofPCAT29 expression under basal condition and reversed the down regulation of this lncRNA by IL-6. Furthermore, we show that knock down ofPCAT29 expression by siRNA in DU145 and LNCaP cells increased cell viability while increasingPCAT29 expression with resveratrol decreased cell viability. Immunohistochemistry studies showed increased levels of STAT3 and IL-6, but low levels of programmed cell death protein 4 (PDCD4), in prostate tumor epithelial cells compared to adjacent perinormal prostate epithelial cells. These data show that the IL-6/STAT3/miR-21 pathway mediates tonic suppression ofPCAT29 expression and function. Inhibition of this signaling pathway by resveratrol inducesPCAT29 expression and tumor suppressor function.
Source: PLoS One - Category: Biomedical Science Authors: Source Type: research