Downregulation of Cdc6 inhibits tumorigenesis of osteosarcoma in vivo and in vitro.

BACKGROUND

Osteosarcoma is the most frequent malignant bone cancer in teenagers. In this study, cell division cycle 6 (Cdc6) was upregulated in the tumor tissues from patients with osteosarcoma according to the results of RNA sequencing. Cdc6 has been considered as a candidate prognostic marker, which was associated with cell apoptosis and cell cycle. However, the mechanisms by which Cdc6 regulates the apoptosis and cell cycle arrest in osteosarcoma remain unclear.

METHODS

Firstly, 3 pairs of osteosarcoma and adjacent normal tissues were subjected to RNA sequencing. In addition, the levels of Cdc6 in 30 pairs of patients' tissues and in osteosarcoma cell lines were detected by western blotting and RT-qPCR. Moreover, the effects of Cdc6 on cell proliferation, apoptosis, cell cycle and invasion were evaluated by cell counting kit-8 (CCK-8), flow cytometric and transwell assay, respectively.

RESULTS

Cdc6 was significantly upregulated in patients with osteosarcoma and in osteosarcoma cell lines. Downregulation of Cdc6 inhibited the proliferation and invasion of MG63 cells by promoting apoptosis. In addition, downregulation of Cdc6 induced G1 phase cell cycle arrest. Moreover, inhibition of Cdc6 downregulated the expression of Cyclin D1 and Cyclin A2, and upregulated the level of p21 in MG63 cells. In vivo study confirmed downregulation of Cdc6 inhibited osteosarcoma tumor growth by inducing apoptosis.

CONCLUSION

Our findings indicated that Cdc6 may serve as an oncogene in osteosarcoma. Thus, inhibiting Cdc6 may be a therapeutic approach for the treatment of osteosarcoma.