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

• Published in: Cancer letters 2017-06, Vol.396, p.66-75
• Main Authors: Zhang, Chun-Lin, Zhu, Kun-Peng, Ma, Xiao-Long
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antibiotics, Antineoplastic - pharmacology; Antisense RNA; Antisense-lncRNA; Bone cancer; Bone Neoplasms - drug therapy; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Cancer; Cell Line, Tumor; Chemotherapy; Child; Cytoplasm; Double-stranded RNA; Doxorubicin; Doxorubicin - pharmacology; Doxorubicin resistance; Drug resistance; Drug Resistance, Neoplasm; Female; Forkhead Transcription Factors - biosynthesis; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; FOXC2-AS1; Gene expression; Hematology, Oncology and Palliative Medicine; Humans; Male; Multidrug resistance; Osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma - genetics; Osteosarcoma - metabolism; Post-transcription; Proteins; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Rodents; Sarcoma; Tissues; Transcription factors; Young Adult
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2017.03.018

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 were 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.