Screening of microRNAs involved in radiation resistance of breast cancer based on bioinformatics

Objective To screen radiotherapy resistance related microRNAs (miRNAs) in breast cancer and provide experimental basis for basic researches and clinical solutions of radiotherapy resistance in breast cancer patients. Methods The miRNA microarray dataset GSE107743 related to breast cancer radiotherapy patients was downloaded from the Gene Expression Omnibus (GEO). The GEO2R analysis tool was used to screen differentially expressed miRNAs in patients with local recurrence after radiotherapy. The target genes of differentially expressed miRNAs were predicted by the mirDIP database. GO enrichment analysis and KEGG pathway analysis on the target genes were performed by DAVID dataset. Finally, differential expression verification was performed in human breast cancer cell line MCF-7 by real-time fluorescent quantitative PCR. Results A total of 9 differentially expressed miRNAs related to radiotherapy resistance were screened by the GEO2R analysis tool, in which three miRNAs (hsa-miR-600, hsa-miR-525-3p and hsa-miR-591) were up-regulated and 6 miRNAs (hsa-miR-488-5p, hsa-miR-582-3p, hsa-miR-520h, hsa-miR-488-3p, hsa-miR-744-3p and hsa-miR-103b) were down-regulated. Target gene prediction results showed that there were 134 potential target genes in these nine differentially expressed miRNAs. These target genes were significantly enriched in related biological processes such as apoptosis and stem cell differentiation (all P<0.05) and signal transduction pathways such as transforming growth factor-β and phosphatidylinositol 3-kinase- protein kinase B signaling pathway (all P<0.05). The results of real-time PCR showed that the differential expression of six miRNAs, i.e. hsa-miR-600, hsa-miR-525-3p, hsa-miR-591, hsa-miR488-5p, hsa-miR-582-3p and hsa-miR-520h, was detected in the MCF-7 cells irradiated by 5 Gy 137Cs γ-rays, and this result was consistent with the results of GEO2R analysis. Conclusion The differentially expressed miRNAs screened from clinical samples of breast cancer patients with local recurrence using bioinformatics may be closely associated with the radiotherapy resistance of these patients. These miRNAs are expected to become new biomarkers for the therapy of radiotherapy resistance. Key words: Breast cancer; Bioinformatics; miRNA; Radiation resistance