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

被引：131

作者：

Misawa, Aya ^{[1
]}

Takayama, Ken-ichi ^{[1
,2
]}

Urano, Tomohiko ^{[1
]}

Inoue, Satoshi ^{[1
,2
,3
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Antiaging Med, Bunkyo Ku, Tokyo 1138655, Japan

[2] Tokyo Metropolitan Inst Gerontol, Dept Funct Biogerontol, Itabashi Ku, 35-2 Sakae Cho, Tokyo 1730015, Japan

[3] Saitama Med Univ, Div Gene Regulat & Signal Transduct, Res Ctr Genom Med, Hidaka, Saitama 3501241, Japan

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2016年 / 291卷 / 34期

基金：

日本学术振兴会;

关键词：

androgen; androgen receptor; apoptosis; long noncoding RNA (lncRNA); prostate cancer; INCREASED SURVIVAL; GENE-EXPRESSION; HUMAN GENOME; RECEPTOR; TRANSCRIPTION; REVEALS; ANTIANDROGEN; SUPPRESSOR; PROGRAM; SOCS-2;

D O I：

10.1074/jbc.M116.718536

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：17861 / 17880

页数：20

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