Antisense lncRNA FOXC2-AS1 promotes doxorubicin resistance in osteosarcoma by increasing the expression of FOXC2.
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.
Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, PR China; Institute of Bone Tumor Affiliated to Tongji University School of Medicine, Shanghai 200072, PR China. Electronic address: shzhangchunlin123@163.com.
Chun-Lin
CL
Zhang
Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, PR China; Institute of Bone Tumor Affiliated to Tongji University School of Medicine, Shanghai 200072, PR China.
Kun-Peng
KP
Zhu
Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, PR China; Institute of Bone Tumor Affiliated to Tongji University School of Medicine, Shanghai 200072, PR China.
Xiao-Long
XL
Ma
D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002648:Child; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D000903:Antibiotics, Antineoplastic; D051858:Forkhead Transcription Factors; D062085:RNA, Long Noncoding; C082078:mesenchyme fork head 1 protein; D004317:Doxorubicin
Antisense-lncRNA; Doxorubicin resistance; FOXC2-AS1; Osteosarcoma