Bioinformatics analysis of dysregulated microRNAs in exosomes from docetaxel-resistant and parental human breast cancer cells
Received 12 January 2019
Accepted for publication 30 April 2019
Published 12 June 2019 Volume 2019:11 Pages 5425—5435
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Rituraj Purohit
Wei-Xian Chen,1,2 Ling-Yun Xu,1 Lin Cheng,1 Qi Qian,1 Xiao He,1 Wen-Ting Peng,1 Yu-Lan Zhu1
1Department of Breast Surgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou 213000, People’s Republic of China; 2Department of Post-doctoral Working Station, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou 213000, People’s Republic of China
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.
Keywords: breast cancer, exosomes, microRNA, chemoresistance, docetaxel
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