In silico Identification of miR-16 Family Target Genes and Pathways Involved in Osteosarcoma Chemoresistance

Abstract Treatment for osteosarcoma (OS) involves surgical resection of the primary tumor followed by chemotherapy to eliminate potential metastases. However, the development of chemoresistance remains a key contributor to the poor prognosis of the disease. In this research, we assessed the effects of miR-16, miR-16-1-3p, and miR-16-2-3p on the sensitivity of OS cells to cisplatin using the SRB cell viability method. Overexpression of these miРНКs in U2OS and HOS cells significantly reduced the 50% inhibitory concentration (IC50) for cisplatin, indicating increased tumor cell sensitivity to this chemotherapy agent. Analysis of RNA-seq data from OS biopsies in the TARGET-OS database identified potential target genes with different expression levels in patients with favorable and unfavorable clinical outcomes. Using the TargetScan 7.2 database, we identified putative targets of miR-16-5p, miR-16-1-3p, and miR-16-2-3p. The intersection of these data allowed us to found subsets of genes whose expression was associated with an unfavorable outcome and could reflect the development of a chemoresistance phenotype. Functional enrichment analysis (GO and KEGG) identified biological processes and signaling pathways potentially involved in the mechanisms of chemoresistance in OS. The results indicate a possible role for miR-16-5p, miR-16-1-3p, and miR-16-2-3p in regulating chemosensitivity in osteosarcoma and their use as prognostic markers of clinical outcome.