Characterization of the Small RNA Transcriptomes of Androgen Dependent and Independent Prostate Cancer Cell Line by Deep Sequencing

Abstract

Given the important roles of miRNA in post-transcriptional regulation and its implications for cancer, characterization of miRNA facilitates us to uncover molecular mechanisms underlying the progression of androgen-independent prostate cancer (PCa). The emergence of next-generation sequencing technologies has dramatically changed the speed of all aspects of sequencing in a rapid and cost-effective fashion, which can permit an unbiased, quantitive and in-depth investigation of small RNA transcriptome. In this study, we used high-throughput Illumina sequencing to comprehensively represent the full complement of individual small RNA and to characterize miRNA expression profiles in both the androgen dependent and independent Pca cell line. At least 83 miRNAs are significantly differentially expressed, of which 41 are up-regulated and 42 are down-regulated, indicating these miRNAs may be involved in the transition of LNCaP to an androgen-independent phenotype. In addition, we have identified 43 novel miRNAs from the androgen dependent and independent PCa library and 3 of them are specific to the androgen-independent PCa. Function annotation of target genes indicated that most of these differentially expressed miRNAs tend to target genes involved in signal transduction and cell communication, epically the MAPK signaling pathway. The small RNA transcriptomes obtained in this study provide considerable insights into a better understanding of the expression and function of small RNAs in the development of androgen-independent prostate cancer.

Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer

“…Regarding PCa, miR-222 has been demonstrated to be highly expressed in androgenindependent PCa cells, compared with androgen-dependent PCa cells. 25,26 miR-222 was also reported to reduce dihydrotestosteroneindependent cell growth by directly targeting the cell cycle inhibitor p27/kip1, suggesting that miR-222 might contribute to the development of castration-resistant PCa. 25 However, several articles also showed downregulation of miR-222 in androgen-dependent PCa cells.…”

Label free quantitative proteomics reveals the role of miR-200b in androgen-independent prostate cancer cells

“…3 Shanghai Applied Protein Technology Co. Ltd, Shanghai 200233, China. 4 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.…”

“…Accumulating evidence indicates that miRNAs play a critical role in AIPC. Previous studies have revealed that miR-200b are down-regulated in AIPC cells and that this phenomenon contributes to androgenindependent growth [3,4]. Functional characterization of miRNAs depends strongly on identification of their specific mRNA binding partners because miRNAs can prevent protein expression by binding either the 3′UTR of the mRNA target through imperfect complementarity or via multiple sites by inhibition of the mRNA interaction with ribosomal complex and the translational machinery [5].…”

MicroRNAs as Regulators of Signal Transduction in Urological Tumors

“…In 4 recent studies investigators performed global comparisons of miRNA patterns in androgendependent vs androgen-independent cells and identified upregulated and downregulated miRNAs (12,(42)(43)(44)(45). A fifth profiling study focused on expression of specific oncogenic clusters and their host genes (miR-17-5pϳ92, miR-106bϳ25, and miR-23bϳ24).…”