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Author Spotlight: RNA FISH for Locating lncRNA-SNHG6 in Osteosarcoma Cells
Published on: June 16, 2023
Antisense lncRNA FOXC2-AS1 promotes doxorubicin resistance in osteosarcoma by increasing the expression of FOXC2
Chun-Lin Zhang1, Kun-Peng Zhu1, Xiao-Long Ma1
1Department 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.
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.
Insights
The long non-coding RNA FOXC2-AS1 promotes doxorubicin resistance in osteosarcoma by increasing FOXC2 expression, which enhances ABCB1 gene expression. This study offers a potential new target for reversing drug resistance in osteosarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Natural antisense long non-coding RNAs (lncRNAs) are critical regulators in cancer biology.
- Doxorubicin resistance is a major challenge in osteosarcoma treatment.
Purpose of the Study:
- To investigate the role of lncRNA FOXC2-AS1 in doxorubicin resistance in osteosarcoma.
- To elucidate the underlying molecular mechanism of FOXC2-AS1 in promoting drug resistance.
Main Methods:
- Analysis of FOXC2-AS1 and FOXC2 expression in doxorubicin-resistant osteosarcoma cell lines and tissues.
- In vitro and in vivo experiments to assess the function of FOXC2-AS1 in doxorubicin resistance.
- Investigation of the interaction between FOXC2-AS1 and FOXC2 at transcriptional and post-transcriptional levels.
- Assessment of the role of FOXC2 in ABCB1 gene expression.
Main Results:
- FOXC2-AS1 and its antisense transcript FOXC2 are upregulated in doxorubicin-resistant osteosarcoma.
- FOXC2-AS1 promotes doxorubicin resistance in vitro and in vivo.
- FOXC2-AS1 regulates FOXC2 expression through an RNA-RNA double-stranded structure.
- FOXC2 contributes to doxorubicin resistance by inducing ABCB1 expression.
Conclusions:
- lncRNA FOXC2-AS1 promotes doxorubicin resistance in osteosarcoma (OS) by upregulating FOXC2 expression, which subsequently enhances ABCB1 expression.
- This mechanism highlights FOXC2-AS1 as a potential therapeutic target for overcoming doxorubicin resistance in OS.
