Exosome-derived microRNAs contribute to prostate cancer chemoresistance.
Certain microRNAs (miRNAs) play a key role in cancer cell chemoresistance. However, the pleiotropic functions of exosome-derived miRNAs on developing chemoresistance remain unknown. In the present study, we aimed to construct potential networks of miRNAs, which derived from the exosome of chemoresistant prostate cancer (PCa) cells, with their known target genes using miRNA expression profiling and bioinformatic tools. Global miRNA expression profiles were measured by microarray. Twelve miRNAs were initially selected and validated by qRT-PCR. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of miRNAs and their targer genes from the selected KEGG pathway 'PCa progression (hsa05215)' were visualized by Cytoscape software. We identified 29 deregulated miRNAs, including 19 upregulated and 10 downregulated, in exosome samples derived from two kinds of paclitaxel resistance PCa cells (PC3-TXR and DU145-TXR) compared with their parental cells (PC3 and DU145). The enrichment results of deregulated miRNAs and known target genes showed that a few pathways were correlated with several critical cell signaling pathways. We found that hub hsa-miR3176, -141-3p, -5004-5p, -16-5p, -3915, -488‑3p, -23c, -3673 and -3654 were potential targets to hub gene androgen receptor (AR) and phosphatase and tensin homolog (PTEN). Hub gene T-cell factors/lymphoid enhancer-binding factors 4 (TCF4) target genes were mainly regulated by hub hsa-miR-32-5, -141-3p, -606, -381 and -429. These results may provide a linkage between PCa chemoresistance and exosome regulatory networks and thus lead us to propose that AR, PTEN and TCF4 genes may be the important genes which are regulated by exosome miRNAs in chemoresistance cancer cells.
Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, P.R. China.
Jing
J
Li
Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, P.R. China.
Xin
X
Yang
Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, P.R. China.
Hao
H
Guan
Department of Urology, Kanazawa University, Kanazawa, Japan.
Atsushi
A
Mizokami
Department of Urology and Pathology, School of Medicine, University of Michigan, Ann Arbor, MI, USA.
Evan T
ET
Keller
Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, P.R. China.
Xiaozhen
X
Xu
Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, P.R. China.
Xia
X
Liu
Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, P.R. China.
Jiyong
J
Tan
Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, P.R. China.
Longyuan
L
Hu
Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, P.R. China.
Yi
Y
Lu
Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, P.R. China.
Jian
J
Zhang
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D055354:Exosomes / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D035683:MicroRNAs; D011944:Receptors, Androgen; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human