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

Al Aameri, Raheem F H ; Sheth, Sandeep ; Alanisi, Entkhab M A ; Borse, Vikrant ; Mukherjea, Debashree ; Rybak, Leonard P ; Ramkumar, Vickram Ahmad, Aamir

PloS one, 2017-05, Vol.12 (5), p.e0177198-e0177198 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Tonic suppression of PCAT29 by the IL-6 signaling pathway in prostate cancer: Reversal by resveratrol
Autor: Al Aameri, Raheem F H ; Sheth, Sandeep ; Alanisi, Entkhab M A ; Borse, Vikrant ; Mukherjea, Debashree ; Rybak, Leonard P ; Ramkumar, Vickram
Ahmad, Aamir
Assuntos: Androgens ; Apoptosis ; Biology and life sciences ; Cancer ; Care and treatment ; Cell death ; Cell growth ; Cell Line, Tumor ; Development and progression ; Epigenetics ; Epithelial cells ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Genes, Tumor Suppressor - physiology ; Health aspects ; Humans ; Immunohistochemistry ; Inhibition ; Interleukin 6 ; Interleukin-6 - physiology ; Male ; Medicine and Health Sciences ; Metastases ; MicroRNAs - physiology ; miRNA ; Physicians ; Physiological aspects ; Prostate cancer ; Prostatic Neoplasms - metabolism ; Real-Time Polymerase Chain Reaction ; Research and analysis methods ; Resveratrol ; Ribonucleic acid ; RNA ; RNA, Long Noncoding - physiology ; Signal transduction ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Signaling ; siRNA ; Stat3 protein ; STAT3 Transcription Factor - physiology ; Stilbenes - pharmacology ; Tissues ; Transcription ; Tumor suppressor genes ; Tumors
É parte de: PloS one, 2017-05, Vol.12 (5), p.e0177198-e0177198
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
Competing Interests: All authors have declared that no competing interests exist for this manuscript.
Conceptualization: VR RA SS.Data curation: RA SS VR.Formal analysis: RA SS.Funding acquisition: VR.Investigation: RA SS EA VB.Methodology: RA SS EA.Project administration: RA.Resources: VR DM LR.Software: VR.Supervision: RA SS VR.Validation: RA VR.Visualization: RA SS.Writing – original draft: RA VR SS.Writing – review & editing: RA VR SS.
Descrição: Prostate cancer (PCa) is the second leading cause of cancer deaths in men. A better understanding of the molecular basis of prostate cancer proliferation and metastasis should enable development of more effective treatments. In this study we focused on the lncRNA, prostate cancer associated transcript 29 (PCAT29), a putative tumor suppressive gene. Our data show that the expression of PCAT29 was reduced in prostate cancer tumors compared to paired perinormal prostate tissues. We also observed substantially lower levels of PCAT29 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 of PCAT29 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 basal PCAT29 expression. In addition, we show that resveratrol is a potent stimulator of PCAT29 expression under basal condition and reversed the down regulation of this lncRNA by IL-6. Furthermore, we show that knock down of PCAT29 expression by siRNA in DU145 and LNCaP cells increased cell viability while increasing PCAT29 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 of PCAT29 expression and function. Inhibition of this signaling pathway by resveratrol induces PCAT29 expression and tumor suppressor function.
Editor: United States: Public Library of Science
Idioma: Inglês

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

Al Aameri, Raheem F H ; Sheth, Sandeep ; Alanisi, Entkhab M A ; Borse, Vikrant ; Mukherjea, Debashree ; Rybak, Leonard P ; Ramkumar, Vickram Ahmad, Aamir

United States: Public Library of Science

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