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.
Highlights
Prostate cancer (PCa) is the most common malignancy of the male genitourinary tract and the third leading cause of cancer death [1,2]
The cells appeared with obvious morphological variations and become small and flat, developing the ability to grow in an androgenindependent fashion (Fig. 1C)
We have identified a large set of miRNAs that are differentially expressed underlying the progression of androgenindependent prostate cancer, which were verified by qRTPCR
Summary
Prostate cancer (PCa) is the most common malignancy of the male genitourinary tract and the third leading cause of cancer death [1,2]. As PCa growth is initially dependent on androgens for survival, androgen deprivation therapy (ADT) has been the mainstay of treatment for PCa. As PCa growth is initially dependent on androgens for survival, androgen deprivation therapy (ADT) has been the mainstay of treatment for PCa These tumors will eventually progress to an androgen-independent phenotype and fail to respond to ADT treatment, becoming the major obstacle of clinical therapy. Understanding the molecular mechanisms that underlie the progression of androgen-independent PCa will shed considerable lights on possible treatment strategies for PCa. miRNAs (microRNAs) are small, non-coding RNA (,20–22 nucleotides) that negatively regulate gene expression at the posttranscriptional level [3]. Given the important roles of miRNAs in post-transcriptional regulation, identification of these differentially expressed and novel miRNAs will facilitate us to uncover the molecular mechanisms underlying the progression of androgen-independent prostate cancer
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