title: Deep sequencing of small RNA libraries from human prostate epithelial and stromal cells reveal distinct pattern of microRNAs primarily predicted to target growth factors.
abstract: Complex epithelial and stromal cell interactions are required during the development and progression of prostate cancer. Regulatory small non-coding microRNAs (miRNAs) participate in the spatiotemporal regulation of messenger RNA (mRNA) and regulation of translation affecting a large number of genes involved in prostate carcinogenesis. In this study, through deep-sequencing of size fractionated small RNA libraries we profiled the miRNAs of prostate epithelial (PrEC) and stromal (PrSC) cells. Over 50 million reads were obtained for PrEC in which 860,468 were unique sequences. Similarly, nearly 76 million reads for PrSC were obtained in which over 1 million were unique reads. Expression of many miRNAs of broadly conserved and poorly conserved miRNA families were identified. Sixteen highly expressed miRNAs with significant change in expression in PrSC than PrEC were further analyzed in silico. ConsensusPathDB showed the target genes of these miRNAs were significantly involved in adherence junction, cell adhesion, EGRF, TGF-β and androgen signaling. Let-7 family of tumor-suppressor miRNAs expression was highly pervasive in both, PrEC and PrSC cells. In addition, we have also identified several miRNAs that are unique to PrEC or PrSC cells and their predicted putative targets are a group of transcription factors. This study provides perspective on the miRNA expression in PrEC and PrSC, and reveals a global trend in miRNA interactome. We conclude that the most abundant miRNAs are potential regulators of development and differentiation of the prostate gland by targeting a set of growth factors. Additionally, high level expression of the most members of let-7 family miRNAs suggests their role in the fine tuning of the growth and proliferation of prostate epithelial and stromal cells.
authors.affiliation: Center of Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Sciences, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Savita
authors.initials: S
authors.lastname: Singh
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology, 727 South Jingming Road, Kunming, Yunnan 650500, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078, USA.
authors.forename: Guru
authors.initials: G
authors.lastname: Jagadeeswaran
authors.affiliation: Center of Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Sciences, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Jey Sabith
authors.initials: JS
authors.lastname: Ebron
authors.affiliation: Department of Biochemistry, Basic Medical Sciences Block-II, Panjab University South Campus, Sector-25, Chandigarh, India.
authors.forename: Kavleen
authors.initials: K
authors.lastname: Sikand
authors.affiliation: Department of Urology, Case Western Reserve University & University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078, USA.
authors.forename: Ramanjulu
authors.initials: R
authors.lastname: Sunker
authors.affiliation: Center of Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Sciences, Cleveland State University, Cleveland, OH 44115, USA. Electronic address: G.shukla@csuohio.edu.
authors.forename: Girish C
authors.initials: GC
authors.lastname: Shukla
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics*; D002460:Cell Line; D016000:Cluster Analysis; D019295:Computational Biology; D030541:Databases, Genetic; D004847:Epithelial Cells / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011467:Prostate / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods*; D017154:Stromal Cells / Q000737:chemistry*
chemical_list: D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs
keywords: Deep sequencing; Prostate cancer; Prostate epithelium; Prostate stromal; microRNA