Antisense lncRNA FOXC2-AS1 promotes doxorubicin resistance in osteosarcoma by increasing the expression of FOXC2

Abstract

Recent efforts have revealed that numerous natural antisense lncRNAs play a crucial role in the regulation of cancer biology. Here, based on our previous study, we further identified that the lncRNA FOXC2-AS1 and its antisense transcript FOXC2 are positively up-regulated in doxorubicin-resistant osteosarcoma cell lines and tissues, correlate with poor prognosis and promote doxorubicin resistance in osteosarcoma cells in vitro and in vivo. In addition, FOXC2-AS1 and FOXC2 are mainly located in the cytoplasm and form an RNA–RNA double-stranded structure in the overlapping region, which is necessary for FOXC2-AS1 to regulate the expression of FOXC2 at both the transcription and post-transcription levels. In addition, transcription factor FOXC2 also contributes to doxorubicin resistance through inducing the expression of the classical multi-drug resistance-related ABCB1 gene similar to FOXC2-AS1. Thus, we concluded that the lncRNA FOXC2-AS1 may promote doxorubicin resistance in OS by increasing the expression of transcription factor FOXC2, further facilitating ABCB1 expression. These findings demonstrate the potential underlying mechanism of FOXC2-AS1 in the regulation of doxorubicin resistance in OS and possibly provide a novel reversing target.