Bioinformatic studying of the miRNA-mRNA related pathways in brain metastatic breast cancer

چکیده مقاله

Introduction: Brain metastasis is one of the main challenges in the treatment process of patients with advanced breast cancer that its molecular basis is not fully understood. Serum miRNAs as new mediators of metastasis have been identified in several cancers and contribute in metastasis related biological pathways. In the present study we aimed to evaluate the miRNA-mRNA related pathways in brain metastatic breast cancer. Methods: miRNA profiling dataset was retrieved from the NCBI Gene Expression Omnibus (GEO) database by accession number GSE134108. This dataset contained 5 serum samples from patients with brain-metastasis and 3 samples of control with no-metastasis. Initial bioinformatics analyses were performed using GEO2R. Top 5 up-regulated miRNAs were assessed by miRwalk web-tool to find their target mRNAs. Moreover related pathways and biological processes were explored using enrichr bioinformatics tool. Results: Our result showed that miR-26b-5p, miR-4633-3p, miR-3651, miR-28-3p and miR-145-5p are 5 top up-regulated miRNAs. Moreover studying the mRNA targets such as CEP78, NOL8, CDC14B, UNC13B, TESK1, CCDC107, ARHGEF39 and CD72 indicated that these microRNAs mostly involved in cell cycle regulation and signal transduction in DNA damage checkpoint. Moreover, our bioinformatic analysis revealed that these genes are correlated with neural system and contribute in neurotransmitter release cycle, synaptic transmission and vesicle-mediated transport in synapse. On the other hands, the target genes are involved in metastasis-related process like cytoskeletal remodeling, cell-extracellular matrix interaction, cell junction organization, cell-cell communication and cell motility. Discussion: These findings specified that miRNA-mRNA interactions might have important roles on both breast cancer progression and brain metastasis. Hence it could be valuable to propose the related hub genes of these interactions as prognostic biomarkers for brain metastasis in breast cancer. Moreover, complementary experimental studies might lead to applying them as therapeutic targets.