The methylated oligonucleotide-induced methylation of DKK3 promoter promotes the malignant properties of osteosarcoma cells.

Background: Deregulation of DKK3 has been reported in various cancers, and its abnormal methylation is closely associated with carcinogenesis. However, the methylation status and function of DKK3 in osteosarcoma have been poorly understood. This study investigated the effects of methylated oligonucleotide-induced methylation of DKK3 promoter on malignant properties of osteosarcoma cells. Methods: SAOS-2 osteosarcoma cells were transfected with methylated or control oligonucleotides. Differences in the methylation status of the DKK3 promoter, proliferation, cell cycle, apoptosis, and metastasis of SAOS-2 cells were compared among the groups treated with different oligonucleotides. Results: The Methylated Oligonucleotide (MON) successfully induced the methylation of the complementary CG sequences in the DKK3 promoter. Viable cells in the MON group were significantly more than that of the control groups. Consistently, in the MON group, the rate of S phase of cells was higher, while the rate of cellular apoptosis was lower than that in control groups. Moreover, the MON could also enhance the metastasis capability of SAOS-2 cells. Conclusion: The methylated oligonucleotide induced the methylation of the DKK3 promoter, and exacerbated the proliferation and metastasis potential of SAOS-2 cells, suggesting that DKK3 promoter methylation could contribute to the malignant transformation of osteosarcoma. Taken together, these findings provide the evidence linking the methylation of the DKK3 promoter to osteosarcoma progression.