The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor

Cui, Zilian; Ren, Shancheng; Lu, Ji; Wang, Fubo; Xu, Weidong; Sun, Yi; Wei, Min; Chen, Junyi; Gao, Xu; Xu, Chuanliang; Mao, Jian-Hua; Sun, Yinghao

doi:10.1016/j.urolonc.2011.11.030

« BackUrologic Oncology: Seminars and Original Investigations

Article in Press

The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor☆

Zilian Cui, M.D., Ph.D.
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
- These authors contributed equally to this article.
Shancheng Ren, M.D., Ph.D.
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
- These authors contributed equally to this article.
Ji Lu, M.S.
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
- These authors contributed equally to this article.
Fubo Wang, M.S.
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
Weidong Xu, M.S.
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
Yi Sun, M.S.
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
Min Wei, M.S.
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
Junyi Chen, Ph.D.
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
Xu Gao, M.D., Ph.D.
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
Chuanliang Xu, M.D., Ph.D.
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
Jian-Hua Mao, Ph.D.
- Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Yinghao Sun, M.D., Ph.D.
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
- Corresponding author. Tel.: +86-21-81873409; fax: +86-21-35030006.

Received 6 August 2011; received in revised form 5 November 2011; accepted 14 November 2011. published online 24 January 2012.
Corrected Proof

Abstract

Objective

Emerging evidences implicate long noncoding RNAs (lncRNAs) are deregulated in cancer development. The purpose of the current study is to investigate the role of new lncRNA, named PlncRNA-1, in prostate cancer (CaP) pathogenesis.

Materials and methods

In this study, real-time q-PCR was used to demonstrate the expression of PlncRNA-1 in 16 pairs CaP tissues and matched normal tissues, 14 pairs CaP tissues and BPH tissues, 4 CaP cell lines, including LNCaP, LNCaP-AI, PC3, and C4-2, and 2 normal prostate epithelial cell lines RWPE-1 and PWR-1E. After PlncRNA-1 was suppressed by siRNA in LNCaP and LNCaP-AI cell lines, cell proliferation and apoptosis were assessed using CCK-8 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). After PlncRNA-1 and AR was suppressed by siRNA in LNCaP and LNCaP-AI cell lines, real-time q-PCR and Western blotting were used to measure reciprocal regulation of PlncRNA-1 and AR.

Results

We showed that expression PlncRNA-1, was significantly higher in CaP cells relative to normal prostate epithelial cells, as well as higher in human CaPs compared with normal tissues and benign prostatic hyperplasia (BPH). Silencing of PlncRNA-1 significantly reduced cell proliferation and induced apoptosis in CaP cell lines LNCaP and LNCaP-AI. Mechanistically, PlncRNA-1 suppression by siRNA resulted in a decrease of androgen receptor (AR) mRNA, protein and AR downstream target. Of note, blockade of AR signaling with siRNA also resulted in a suppression of PlncRNA-1 expression in CaP cell lines.

Conclusions

Our study suggests reciprocal regulation of PlncRNA-1 and androgen receptor contribute to CaP pathogenesis and that PlncRNA-1 is a potential therapy target.

Keywords: Long noncoding RNA , Androgen receptor , Prostate cancer

To access this article, please choose from the options below

☆ This work was supported by funding from The National “11th five” Major Research Grant for Creating New Drugs (no. 2009ZX09312-025, Y.H.S), Ministry of Science and Technology of Shanghai (no. 08410701500, Y.H.S).