Background: Osteosarcoma (OS), an aggressive malignant neoplasm, exhibits osteoblastic differentiation. Cisplatin (DDP) and taxanes are among the most effective drugs for OS patients. Nevertheless, the drug resistance remains a main limitation to efficacious chemotherapy in OS. The current report sets to explore the biological function of microRNA-584 (miR-584) and the potential mechanism underlying OS cells resistance to these two drugs.
Materials and Methods: The expression profiles of miR-584 and connective tissue growth factor (CTGF, CCN2) in OS tissue samples and cell lines were tested by means of reverse transcription-quantitative polymerase chain reaction and Western blot. U2OS and MG63 cell lines were delivered with miR-584 mimic alone or plus CCN2 to excavate theirs functions by cell counting kit-8 and EdU, flow cytometric analysis, as well as transwell assay, severally. Western bot analysis was conducted to examine the expression of IκBα, pIκBα, NF-κB and pNF-κB. Dual-luciferase reporter gene assay was carried out to assess the targets of miR-584.
Results: The downregulation of miR-584 was identified in OS tissues and cells, which was closely linked to the dismal prognosis of OS patients. Overexpression of miR-584 repressed cell viability, migration as well as invasion, potentiated apoptosis and sensitized OS cells to DDP and taxanes. Mechanism investigation specified a direct targeting relationship between CCN2 and miR-584 in OS.
Conclusion: In conclusion, miR-584 has the potency to act as a therapeutic maneuver for OS mainly by inducing the chemosensitivity of OS cells to DDP and taxanes.
Keywords: osteosarcoma, microRNA-584, CCN2, the IκBα/NF-κB signaling pathway, chemoresistance