title: Screening key microRNAs for castration-resistant prostate cancer based on miRNA/mRNA functional synergistic network.
abstract: High-throughput methods have been used to explore the mechanisms by which androgen-sensitive prostate cancer (ASPC) develops into castration-resistant prostate cancer (CRPC). However, it is difficult to interpret cryptic results by routine experimental methods. In this study, we performed systematic and integrative analysis to detect key miRNAs that contribute to CRPC development. From three DNA microarray datasets, we retrieved 11 outlier microRNAs (miRNAs) that had expression discrepancies between ASPC and CRPC using a specific algorithm. Two of the miRNAs (miR-125b and miR-124) have previously been shown to be related to CRPC. Seven out of the other nine miRNAs were confirmed by quantitative PCR (Q-PCR) analysis. MiR-210, miR-218, miR-346, miR-197, and miR-149 were found to be over-expressed, while miR-122, miR-145, and let-7b were under-expressed in CRPC cell lines. GO and KEGG pathway analyses revealed that miR-218, miR-197, miR-145, miR-122, and let-7b, along with their target genes, were found to be involved in the PI3K and AKT3 signaling network, which is known to contribute to CRPC development. We then chose five miRNAs to verify the accuracy of the analysis. The target genes of each miRNA were altered significantly upon transfection of specific miRNA mimics in the C4-2 CRPC cell line, which was consistent with our pathway analysis results. Finally, we hypothesized that miR-218, miR-145, miR-197, miR-149, miR-122, and let-7b may contribute to the development of CRPC through the influence of Ras, Rho proteins, and the SCF complex. Further investigation is needed to verify the functions of the identified novel pathways in CRPC development.
authors.affiliation: Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China.|Department of Urology, Huai'an Hospital Affiliated to Xuzhou Medical College and Second People's Hospital of Huai'an, Huai'an, China.
authors.forename: Sugui
authors.initials: S
authors.lastname: Wang
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Dongrong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, China.
authors.forename: Bairong
authors.initials: B
authors.lastname: Shen
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D020411:Oligonucleotide Array Sequence Analysis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: bioinformatics model; castration-resistant prostate cancer; microRNA biomarker; microRNA-mRNA interaction; pathway analysis