Oncotarget

Research Papers:

Screening key microRNAs for castration-resistant prostate cancer based on miRNA/mRNA functional synergistic network

Jin Zhu _, Sugui Wang, Wenyu Zhang, Junyi Qiu, Yuxi Shan, Dongrong Yang and Bairong Shen

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:43819-43830. https://doi.org/10.18632/oncotarget.6102

Metrics: PDF 1099 views  |   HTML 1445 views  |   ?  


Abstract

Jin Zhu1,*, Sugui Wang1,2,*, Wenyu Zhang3,*, Junyi Qiu4, Yuxi Shan1, Dongrong Yang1, Bairong Shen3

1Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China

2Department of Urology, Huai’an Hospital Affiliated to Xuzhou Medical College and Second People’s Hospital of Huai’an, Huai’an, China

3Center for Systems Biology, Soochow University, Suzhou, China

4Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China

*These authors have contributed equally to this work

Correspondence to:

Dongrong Yang, e-mail: doc_ydr@163.com

Bairong Shen, e-mail: bairong.shen@suda.edu.cn

Keywords: castration-resistant prostate cancer, microRNA biomarker, microRNA-mRNA interaction, bioinformatics model, pathway analysis

Received: May 04, 2015     Accepted: October 17, 2015     Published: October 31, 2015

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 6102