Identification of androgen-responsive lncRNAs as diagnostic and prognostic markers for prostate cancer
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Xuechao Wan1,*, Wenhua Huang1,*, Shu Yang1, Yalong Zhang1, Honglei Pu1, Fangqiu Fu1, Yan Huang1, Hai Wu1, Tao Li3, Yao Li1,2
1State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center Of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, PR China
2Key Laboratory of Reproduction Regulation of NPFPC, Fudan University, Shanghai 200433, PR China
3Department of Urology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200433, PR China
*These authors contributed equally to this work
Yao Li, email: firstname.lastname@example.org
Tao Li, email: email@example.com
Keywords: long non-coding RNA, prostate cancer, androgen receptor, expression profiling, biomarkers
Received: September 24, 2015 Accepted: July 26, 2016 Published: August 19, 2016
Prostate cancer (PCa) is a leading cause of mortality among males. Long non-coding RNAs (lncRNAs) are subclass of noncoding RNAs that may act as biomarkers and therapeutic targets. In this study, we firstly conducted analysis of global lncRNA expression patterns by using our own cohort (GSE73397) and two public available gene expression datasets: The Cancer Genome Atlas (TCGA) and GSE55909. Next, we performed microarray to observe genome-wide lncRNAs’ expressions under dihydrotestosterone (DHT) stimulation in LNCaP cells (GSE72866), and overlapped the result with ChIPBase data to predict androgen-responsive lncRNAs with ARE. Combined the two results, a total of 44 androgen-responsive lncRNAs with ARE were found to be over-expressed in PCa samples. Ten lncRNAs were selected for further validation by examining their expressions in LNCaP cells under DHT stimulation, and in PCa samples and cell lines. Among them, RP1-4514.2, LINC01138, SUZ12P1 and KLKP1 were validated as directly AR-targeted lncRNAs by ChIP-PCR. Then we conducted a bioinformatic analysis to identify lncRNAs as putative prognostic and therapeutic targets by using TCGA data. Three androgen-responsive lncRNAs, LINC01138, SUZ12P1 and SNHG1 showed association with gleason score and pT-stage. The biological functions of LINC01138 and SUZ12P1 were also evaluated, both lncRNAs promoted the proliferation and inhibited apoptosis of PCa. These results provide potent information for exploring potential biomarkers and therapeutic targets for prostate cancer, especially for castration-resistant PCa.
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