LncRNA FGD5‐AS1 potentiates autophagy‐associated doxorubicin resistance by regulating the miR‐154‐5p/WNT5A axis in osteosarcoma

Osteosarcoma is prevalent in children and adolescent. The oncogenic function of long‐chain noncoding RNA (lncRNA) FGD5 antisense RNA 1 (FGD5‐AS1) has been reported. However, the function of FGD5‐AS1 in doxorubicin‐resistance in osteosarcoma remains to be illucidated. Quantitative real‐time PCR (qRT‐PCR) and western blot analysis (WB) were used to measure the expression of FGD5‐AS1, miR‐154‐5p, WNT5A and autophagy proteins. MTT assay was used to assess cell viability and transwell assay was performed to evaluate migration. A nude mouse xenograft model was developed to verify the function of FGD5‐AS1 in vivo. FGD5‐AS1 was upregulated in doxorubicin‐resistant (DXR) osteosarcoma cells. Knockdown of FGD5‐AS1 suppressed osteosarcoma cell proliferation, migration, and autophagy. FGD5‐AS1 upregulated WNT5A expression via sponging miR‐154‐5p. Furthermore, FGD5‐AS1 enhanced osteosarcoma cell chemotherapy resistance through upregulation of WNT5A by inhibiting miR‐154‐5p. Suppression of FGD5‐AS1 significantly suppressed tumor growth in nude mice. FGD5‐AS1 may promote chemoresistance through WNT5A‐induced autophagy by sponging miR‐154‐5p in osteosarcoma cells.

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