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Bioinformatics analysis of dysregulated microRNAs in exosomes from docetaxel-resistant and parental human breast cancer cells
- Source :
- Cancer Management and Research. 11:5425-5435
- Publication Year :
- 2019
- Publisher :
- Informa UK Limited, 2019.
-
Abstract
- Background: Resistance to docetaxel is a major obstacle to effective treatment of breast cancer. Exosomal microRNAs (miRNAs) have recently been introduced in cell-to-cell transmission of chemoresistance between heterogeneous populations of tumor cells with diverse drug sensitivity. However, a systematic evaluation of the exosomal miRNA signature remains largely unclear. Method: miRNA expression profiles in exosomes from docetaxel-resistant (D/exo) and parental sensitive breast cancer cells (S/exo) were assessed using microarray. Bioinformatics analysis was performed to predict target genes of the dysregulated miRNAs and to uncover their potential roles in chemoresistance formation. Signaling pathways, gene ontology terms, transcription factors, protein-protein interactions, and hub genes were also constructed. Results: The selected exosomal miRNAs could modulate target genes responsible for MAPK, TGF-beta, Wnt, mTOR, and PI3K/Akt signaling pathways. Function enrichment analysis revealed the involvement of target genes in transcription regulation, protein phosphorylation, kinase activity, and protein binding. Enriched transcription factors including SP1, SP4, and EGR1 were obtained and a protein-protein interaction network was established. The hub genes for up-expressed and down-expressed exosomal miRNAs such as CCND1 and PTEN were identified. Conclusion: This bioinformatics study provides a comprehensive view of the function of dysregulated exosomal miRNAs, and may help us to understand exosome-mediated resistance transmission and overcome docetaxel resistance in future breast cancer therapy.
- Subjects :
- 0301 basic medicine
biology
Wnt signaling pathway
Microvesicles
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Oncology
030220 oncology & carcinogenesis
microRNA
Cancer cell
Cancer research
biology.protein
PTEN
Kinase activity
Transcription factor
PI3K/AKT/mTOR pathway
Subjects
Details
- ISSN :
- 11791322
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cancer Management and Research
- Accession number :
- edsair.doi...........fa5dd02ec77c9488ecb8929e4560f9cc