Androgen-induced Long Noncoding RNA (lncRNA) SOCS2-AS1 Promotes Cell Growth and Inhibits Apoptosis in Prostate Cancer Cells

Long noncoding RNAs (lncRNA) have been associated with the development of cancer. However, the interplay between lncRNAs and androgen receptor (AR) signaling in prostate cancer is still unclear. Here, we identified lncRNAs induced by androgen in AR-positive prostate cancer cells, where induction was...

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Published inThe Journal of biological chemistry Vol. 291; no. 34; pp. 17861 - 17880
Main Authors Misawa, Aya, Takayama, Ken-ichi, Urano, Tomohiko, Inoue, Satoshi
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 19.08.2016
American Society for Biochemistry and Molecular Biology
Subjects
androgen
androgen receptor
Androgens - pharmacology
apoptosis
Apoptosis - drug effects
Cell Line, Tumor
Epigenesis, Genetic - drug effects
Epigenesis, Genetic - genetics
Gene Expression Regulation, Neoplastic - drug effects
Gene Expression Regulation, Neoplastic - genetics
Gene Regulation
Humans
long noncoding RNA (lncRNA)
Male
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
prostate cancer
Prostatic Neoplasms, Castration-Resistant - genetics
Prostatic Neoplasms, Castration-Resistant - metabolism
Prostatic Neoplasms, Castration-Resistant - pathology
Receptors, Androgen - biosynthesis
Receptors, Androgen - genetics
RNA, Long Noncoding - biosynthesis
RNA, Long Noncoding - genetics
RNA, Neoplasm - biosynthesis
RNA, Neoplasm - genetics
Signal Transduction - drug effects
Signal Transduction - genetics
TNF-Related Apoptosis-Inducing Ligand - biosynthesis
TNF-Related Apoptosis-Inducing Ligand - genetics
Up-Regulation - drug effects
Up-Regulation - genetics
long noncoding RNA (lncRNA)
apoptosis
androgen
prostate cancer
androgen receptor
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Abstract Long noncoding RNAs (lncRNA) have been associated with the development of cancer. However, the interplay between lncRNAs and androgen receptor (AR) signaling in prostate cancer is still unclear. Here, we identified lncRNAs induced by androgen in AR-positive prostate cancer cells, where induction was abolished by AR knockdown as well as an anti-androgen, bicalutamide. By combining these data, we identified an androgen-regulated lncRNA, suppressor of cytokine signaling 2-antisense transcript 1 (SOCS2-AS1), the expression of which was higher in castration-resistant prostate cancer model cells, i.e. long-term androgen-deprived (LTAD) cells, than in parental androgen-dependent LNCaP cells. SOCS2-AS1 promoted castration-resistant and androgen-dependent cell growth. We found that SOCS2-AS1 knockdown up-regulated genes related to the apoptosis pathway, including tumor necrosis factor superfamily 10 (TNFSF10), and sensitized prostate cancer cells to docetaxel treatment. Moreover, we also demonstrated that SOCS2-AS1 promotes androgen signaling by modulating the epigenetic control for AR target genes including TNFSF10. These findings suggest that SOCS2-AS1 plays an important role in the development of castration-resistant prostate cancer by repressing apoptosis.
AbstractList Long noncoding RNAs (lncRNA) have been associated with the development of cancer. However, the interplay between lncRNAs and androgen receptor (AR) signaling in prostate cancer is still unclear. Here, we identified lncRNAs induced by androgen in AR-positive prostate cancer cells, where induction was abolished by AR knockdown as well as an anti-androgen, bicalutamide. By combining these data, we identified an androgen-regulated lncRNA, suppressor of cytokine signaling 2-antisense transcript 1 (SOCS2-AS1), the expression of which was higher in castration-resistant prostate cancer model cells, i.e long-term androgen-deprived (LTAD) cells, than in parental androgen-dependent LNCaP cells. SOCS2-AS1 promoted castration-resistant and androgen-dependent cell growth. We found that SOCS2-AS1 knockdown up-regulated genes related to the apoptosis pathway, including tumor necrosis factor superfamily 10 (TNFSF10), and sensitized prostate cancer cells to docetaxel treatment. Moreover, we also demonstrated that SOCS2-AS1 promotes androgen signaling by modulating the epigenetic control for AR target genes including TNFSF10 These findings suggest that SOCS2-AS1 plays an important role in the development of castration-resistant prostate cancer by repressing apoptosis.
Long noncoding RNAs (lncRNA) have been associated with the development of cancer. However, the interplay between lncRNAs and androgen receptor (AR) signaling in prostate cancer is still unclear. Here, we identified lncRNAs induced by androgen in AR-positive prostate cancer cells, where induction was abolished by AR knockdown as well as an anti-androgen, bicalutamide. By combining these data, we identified an androgen-regulated lncRNA, suppressor of cytokine signaling 2-antisense transcript 1 ( SOCS2-AS1 ), the expression of which was higher in castration-resistant prostate cancer model cells, i.e . long-term androgen-deprived (LTAD) cells, than in parental androgen-dependent LNCaP cells. SOCS2-AS1 promoted castration-resistant and androgen-dependent cell growth. We found that SOCS2-AS1 knockdown up-regulated genes related to the apoptosis pathway, including tumor necrosis factor superfamily 10 ( TNFSF10 ), and sensitized prostate cancer cells to docetaxel treatment. Moreover, we also demonstrated that SOCS2-AS1 promotes androgen signaling by modulating the epigenetic control for AR target genes including TNFSF10 . These findings suggest that SOCS2-AS1 plays an important role in the development of castration-resistant prostate cancer by repressing apoptosis.
Long noncoding RNAs (lncRNA) have been associated with the development of cancer. However, the interplay between lncRNAs and androgen receptor (AR) signaling in prostate cancer is still unclear. Here, we identified lncRNAs induced by androgen in AR-positive prostate cancer cells, where induction was abolished by AR knockdown as well as an anti-androgen, bicalutamide. By combining these data, we identified an androgen-regulated lncRNA, suppressor of cytokine signaling 2-antisense transcript 1 (SOCS2-AS1), the expression of which was higher in castration-resistant prostate cancer model cells, i.e long-term androgen-deprived (LTAD) cells, than in parental androgen-dependent LNCaP cells. SOCS2-AS1 promoted castration-resistant and androgen-dependent cell growth. We found that SOCS2-AS1 knockdown up-regulated genes related to the apoptosis pathway, including tumor necrosis factor superfamily 10 (TNFSF10), and sensitized prostate cancer cells to docetaxel treatment. Moreover, we also demonstrated that SOCS2-AS1 promotes androgen signaling by modulating the epigenetic control for AR target genes including TNFSF10 These findings suggest that SOCS2-AS1 plays an important role in the development of castration-resistant prostate cancer by repressing apoptosis.Long noncoding RNAs (lncRNA) have been associated with the development of cancer. However, the interplay between lncRNAs and androgen receptor (AR) signaling in prostate cancer is still unclear. Here, we identified lncRNAs induced by androgen in AR-positive prostate cancer cells, where induction was abolished by AR knockdown as well as an anti-androgen, bicalutamide. By combining these data, we identified an androgen-regulated lncRNA, suppressor of cytokine signaling 2-antisense transcript 1 (SOCS2-AS1), the expression of which was higher in castration-resistant prostate cancer model cells, i.e long-term androgen-deprived (LTAD) cells, than in parental androgen-dependent LNCaP cells. SOCS2-AS1 promoted castration-resistant and androgen-dependent cell growth. We found that SOCS2-AS1 knockdown up-regulated genes related to the apoptosis pathway, including tumor necrosis factor superfamily 10 (TNFSF10), and sensitized prostate cancer cells to docetaxel treatment. Moreover, we also demonstrated that SOCS2-AS1 promotes androgen signaling by modulating the epigenetic control for AR target genes including TNFSF10 These findings suggest that SOCS2-AS1 plays an important role in the development of castration-resistant prostate cancer by repressing apoptosis.
Author Urano, Tomohiko
Misawa, Aya
Takayama, Ken-ichi
Inoue, Satoshi
Author_xml – sequence: 1
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  surname: Misawa
  fullname: Misawa, Aya
  organization: Department of Anti-aging Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
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  givenname: Ken-ichi
  surname: Takayama
  fullname: Takayama, Ken-ichi
  organization: Department of Anti-aging Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
– sequence: 3
  givenname: Tomohiko
  surname: Urano
  fullname: Urano, Tomohiko
  organization: Department of Anti-aging Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
– sequence: 4
  givenname: Satoshi
  surname: Inoue
  fullname: Inoue, Satoshi
  email: sinoue@tmig.or.jp
  organization: Department of Anti-aging Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
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2016 by The American Society for Biochemistry and Molecular Biology, Inc.
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Keywords long noncoding RNA (lncRNA)
apoptosis
androgen
prostate cancer
androgen receptor
Language English
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2016 by The American Society for Biochemistry and Molecular Biology, Inc.
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Snippet Long noncoding RNAs (lncRNA) have been associated with the development of cancer. However, the interplay between lncRNAs and androgen receptor (AR) signaling...
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SubjectTerms androgen
androgen receptor
Androgens - pharmacology
apoptosis
Apoptosis - drug effects
Cell Line, Tumor
Epigenesis, Genetic - drug effects
Epigenesis, Genetic - genetics
Gene Expression Regulation, Neoplastic - drug effects
Gene Expression Regulation, Neoplastic - genetics
Gene Regulation
Humans
long noncoding RNA (lncRNA)
Male
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
prostate cancer
Prostatic Neoplasms, Castration-Resistant - genetics
Prostatic Neoplasms, Castration-Resistant - metabolism
Prostatic Neoplasms, Castration-Resistant - pathology
Receptors, Androgen - biosynthesis
Receptors, Androgen - genetics
RNA, Long Noncoding - biosynthesis
RNA, Long Noncoding - genetics
RNA, Neoplasm - biosynthesis
RNA, Neoplasm - genetics
Signal Transduction - drug effects
Signal Transduction - genetics
TNF-Related Apoptosis-Inducing Ligand - biosynthesis
TNF-Related Apoptosis-Inducing Ligand - genetics
Up-Regulation - drug effects
Up-Regulation - genetics
Title Androgen-induced Long Noncoding RNA (lncRNA) SOCS2-AS1 Promotes Cell Growth and Inhibits Apoptosis in Prostate Cancer Cells
URI https://dx.doi.org/10.1074/jbc.M116.718536
https://www.ncbi.nlm.nih.gov/pubmed/27342777
https://www.proquest.com/docview/1812888620
https://pubmed.ncbi.nlm.nih.gov/PMC5016176
Volume 291
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