Identification of the key miRNA; hsa-miR-1269a targeting TP53, Caspase-9 and FOXO3a in breast cancer cells under hypoxia by integrated bioinformatics analysis

Abstract

BackgroundHypoxia microenvironment allied too many vital events relevant to tumorigenesis such as; proliferation, speedy angiogenesis, metastasis, poor prognosis and resistance to several anticancer therapies. miRNAs are established as key players during cellular adaptations in metabolism, proliferation, DNA repair, and apoptosis in various cancer including breast cancer under hypoxia. However, the results have been unsatisfactory so far supporting the need of identifying novel players in hypoxia signaling that can be an ideal candidate for breast cancer therapy. ObjectiveThe current study aimed to find out the DE miRNAs and their target mRNAs/genes related to breast cancer progression and metastasis under hypoxia via in silico analysis. MethodsBased on microarray analysis of DE miRNAs, a string of computational approaches was used to select the most prominent hypoximiRs and their targets. Targets of these DE miRNAs were identified by using miRDB and TargetScan v7.2. Simultaneously miRNA enrichment and GO analysis were utilized to select their associated biological pathways. Further sequence alignment, molecular docking and semiquantitative RT-PCR were performed to select the most suitable targets of candidate miRNA. ResultsThe combined study of GO, KEGG, and miRNAs-mRNAs network analysis pragmatically demonstrated that hsa-miR-1269a and its selected target genes (TP53, Caspase-9, and FOXO3a) show maximum interaction with other miRNAs and shared common interaction pathways. Sequence alignment, molecular docking and RT-PCR further confirmed the targets of hsa-miR-1269a and revealed that it may inhibit cell growth by promoting apoptosis. ConclusionOur findings concluded that, TP53, Caspase-9 and FOXO3a could be the probable targets of hsa-miR-1269a that ultimately promotes breast cancer cells survival and proliferation under hypoxia. In conclusion, this computational study eventually suggest that, hsa-miR-1269a could be considered as a valuable prognostic marker for breast cancer therapeutics.