Effect of lncRNA ANRIL knockdown on proliferation and cisplatin chemoresistance of osteosarcoma cells in vitro.

Chemoresistance is a major obstacle in treating cancer, including osteosarcoma. LncRNA ANRIL (ANRIL) is involved in the growth and metastasis of osteosarcoma cells, however, its role in chemoresistance remains unclear. In this study, ANRIL shRNA was used to knock down its endogenous expression in U2-OS and Saos-2 osteosarcoma cell lines. Our data showed that ANRIL-silenced cells were more sensitive to cisplatin: apoptotic ratio was increased and cleaved caspase-3 level was upregulated. Furthermore, the expression level of miR-125a-5p, a microRNA that can bind to ANRIL, was elevated in ANRIL-silenced cells. MiR-125a-5p inhibitor attenuated ANRIL knockdown-induced chemosensitivity to cisplatin. In addition, ANRIL knockdown resulted in a reduction in STAT3, a target of miR-125a-5p, in osteosarcoma cells. Forced overexpression of STAT3 weakened the chemosensitivity of ANRIL-silenced cells to cisplatin. In conclusion, our study demonstrates that ANRIL knockdown sensitizes osteosarcoma cells to cisplatin-induced cytotoxicity, suggesting ANRIL as a therapeutic target for osteosarcoma chemotherapy.