TFAP2C-mediated LINC00922 signaling underpins doxorubicin-resistant osteosarcoma

Abstract

Long noncoding RNAs (lncRNAs) have been indicated as critical regulators in osteosarcoma (OS). However, the function of lncRNAs in doxorubicin (DXR)-resistant OS remain unclear. Here, present study investigated the functions of lncRNA LINC00922 on the DXR resistance in OS tumorigenesis. LncRNA expression profile was detected using lncRNA microarray in DXR-resistant OS cells (MG63/DXR) and parental cells (MG63). Molecular binding was detected using luciferase reporter assay and chromatin immunoprecipitation. DXR sensitivity assay was detected using CCK-8 assay. Results showed that LINC00922 was significantly up-regulated in OS tissue specimens. Cellular assays showed that LINC00922 increased DXR IC50 and the knockdown of LINC00922 repressed the tumor growth of OS cells. Mechanistic assays showed that LINC00922 acts as a sponge of miR-424-5p, and miR-424-5p targeted the 3'-untranslated region of transcription factor activating protein 2 gamma (TFAP2C) mRNA. Moreover, TFAP2C promoted transcription of LINC00922 in a positive feedback loop comprising TFAP2C, LINC00922, and miR-424-5p. Collectively, these findings uncovered the function of TFAP2C/LINC00922/miR-424-5p feedback loop in DXR resistance, suggesting new therapeutic direction for OS.

Keywords

• Doxorubicin-resistance
• LINC00922
• Osteosarcoma
• TFAP2C