Interleukin-6 upregulates SOX18 expression in osteosarcoma

SOX18 is a potential oncogene in osteosarcoma via controlling osteosarcoma cell proliferation and metastasis. Interleukin-6 (IL-6), a major activator of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling, plays an important role in the growth of carcinoma cells. The present study aims to investigate the correlation between IL-6 and SOX18 in osteosarcoma.

Protein expression and mRNA expression were determined by Western blot and real-time polymerase chain reaction (PCR) analysis, respectively. Cell proliferation and apoptosis were identified by Cell Counting Kit-8 assay and flow cytometry analysis, respectively.

We found that SOX18, IL-6 and p-STAT3 were elevated in osteosarcoma compared with bone cyst tissues. A positive correlation between the mRNA levels of IL-6 and SOX18 was observed in osteosarcoma tissues. IL-6 stimulation dose dependently induced the mRNA and protein levels of SOX18 in U-2OS and MG63 cells. Furthermore, IL-6 significantly rescued the inhibitory and induction effects of SOX18 knockdown on osteosarcoma cell proliferation and apoptosis, respectively. The changes in cell proliferation (PCNA) and apoptosis-related proteins (Bcl-2, Bax and Cleaved-Caspase 3) were in line with the results of cell proliferation and apoptosis assays.

Our data suggest that IL-6 is a possible upstream regulator for SOX18 in osteosarcoma.