Downregulation of miR-19a inhibits the proliferation and promotes the apoptosis of osteosarcoma cells by regulating the JAK2/STAT3 pathway.

Abstract

Osteosarcoma is a malignant tumor derived from the skeletal system, often occurring in bone tissues, and it is the most common malignant tumor in the skeletal system, with more than 90% of cases being highly malignant. The present study was designed to explore the regulatory effects of microRNA (miR)-19a on the proliferation and apoptosis of osteosarcoma cells, and its influence on the activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. The expression of miR-19a in adult SaOS-2 osteosarcoma cells was downregulated via lentiviral transfection, and the cells were divided into a control group, NC-inhibitor group and miR-19a-inhibitor group. The expression of miR-19a in each group was detected via quantitative polymerase Chain reaction (qPCR). Next, the cell proliferation and apoptosis levels in each group were detected via methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively, and the level of reactive oxygen species (ROS) in cells was further determined. Moreover, the expression levels of apoptosis-related proteins and JAK2/STAT3 signaling pathway-related proteins were detected through western blotting. The expression level of miR-19a in the miR-19a-inhibitor group was significantly lower than that in the control group and NC-inhibitor group (P<0.01). Downregulation of miR-19a significantly reduced the proliferation ability (P<0.01), increased the apoptosis level of SaOS-2 cells (P<0.01), and significantly increased the ROS level in cells (P<0.01). Downregulation of miR-19a also promote cleaved caspase-3/caspase-3 expression in the OS cells (P<0.01) and inhibited Bcl-2/Bax expression (P<0.01). Additionally, downregulation of miR-19a markedly lowered the protein expression levels of phosphorylated (p-)JAK2, p-STAT3 and myeloid cell leukemia-1 (Mcl-1) in the cells (P<0.01). To conclude, downregulation of miR-19a can inhibit the JAK2/STAT3 signaling pathway in SaOS-2 cells, promote the expression of apoptosis-related proteins, and increase the ROS level in cells, thereby promoting apoptosis and inhibiting cell proliferation.