Expression profile analysis of microRNAs in prostate cancer by next-generation sequencing

Abstract

Purpose: Prostate cancer (PCa) is the second leading cause of tumor mortality among males in western societies. In China, the diagnostic and fatality rate of PCa is increasing yearly. MicroRNAs (miRNAs) are small single stranded non-coding RNA molecules (~22 nucleotides) which impede protein production by directly interacting with 3’-untranslated regions of the target mRNAs. miRNAs are crucial regulators in malignant tumors. Recent profiling research suggests that miRNAs are aberrantly expressed in PCa, and these have been implicated in the regulation of apoptosis, cell cycle, epithelial to mesenchymal transition, PCa stem cells, and androgen receptor pathway.

Methods: To find miRNAs differentially expressed in PCa and their relation to prognostic factors and therapeutic potentials, we studied 24 surgical specimens from men who underwent radical prostatectomy, through high-throughput Illumina sequencing and quantitative real-time PCR (qRT-PCR) methods. Moreover, a variety of biological information softwares and databases were applied to predict the target genes of miRNA, molecular functions, and signal pathways. We also discuss the functional significance of the differentially expressed miRNAs and the molecular pathways/targets regulated by these miRNAs.

Results: Many miRNAs were differentially expressed (fold change 2, P<0.05) by sequencing. This was confirmed by qRT-PCR in more clinical tissue samples. In the tumors, miRNAs (miR-125b-5p, miR-126-5p, miR-141, miR-151a-5p, miR-221-3p and miR-222-3p) were significantly upregulated with downregulation of miR-486-5p and miR-488. In addition, 13 novel miRNAs were identified from three prostate tissue libraries, with 12 of them assayed in 21 human normal tissues by qRT-PCR. Multiple databases indicated target genes for these differentially expressed miRNAs. Function annotation of target genes indicated that most of them tend to target genes involved in signal transduction and cell communication, especially cancer-related PI3K-Akt and p53 signaling pathway. Moreover, miR-141 and miR-488 post-transcriptionally regulated androgen receptor (AR) expression, and inhibited the growth and metastasis of prostate gland epithelial cells.

Conclusion: The small RNA transcriptomes obtained in this study uncovers the differentially expressed miRNAs, and provides a better understanding of the expression and function of miRNAs in the development of PCa and reveals several miRNAs in PCa that may have biomarker and therapeutic potentials.

-----------------------------------------

Cite this article as:  Song C, Chen H, Ru G, Ding Q, Yang W. Expression profile analysis of microRNAs in prostate cancer by next-generation sequencing. Int J Cancer Ther Oncol 2015; 3(4):3405.

[This abstract was presented at the BIT’s 8^th Annual World Cancer Congress, which was held from May 15-17, 2015 in Beijing, China.]