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Author Spotlight: Replicating Human Osteosarcoma Progression in Immunodeficient Mice for Cancer Study
Published on: March 22, 2024
A long non-coding RNA contributes to doxorubicin resistance of osteosarcoma
Chun-Lin Zhang1, Kun-Peng Zhu2, Guo-Qi Shen3
1Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, 301, Yan-chang Middle Road, Shanghai, 200072, People's Republic of China. shzhangchunlin123@163.com.
Abstract:
Long non-coding RNAs (lncRNAs) are emerging in molecular biology as crucial regulators of cancer. Although the aberrant expression of lncRNAs has been observed in osteosarcoma (OS), the molecular mechanisms underlying lncRNAs in doxorubicin resistance of OS still unknown. In the current study, we investigated a novel lncRNA, termed ODRUL (osteosarcoma doxorubicin-resistance related up-regulated lncRNA), and evaluated its role in the occurrence of doxorubicin resistance in OS. LncRNA microarray revealed that lncRNA ODRUL was the most up-regulated expressed in the doxorubicin-resistant OS cell line. Quantitative real-time PCR (qRT-PCR) confirmed that lncRNA ODRUL was higher in different doxorubicin-resistant OS cell lines and lower in different doxorubicin-sensitive OS cell lines. Moreover, we showed that lncRNA ODRUL was increased in specimens of OS patients with a poor chemoresponse and lung metastasis. We further demonstrated that lncRNA ODRUL inhibition could inhibit OS cell proliferation, migration, and partly reversed doxorubicin resistance in vitro. In addition, we found that the expression of classical drug resistance-related ATP-binding cassette, subfamily B, member 1 (ABCB1) gene was decreased after the lncRNA ODRUL knockdown. Thus, we concluded that lncRNA ODRUL may act as a pro-doxorubicin-resistant molecule through inducing the expression of the classical multidrug resistance-related ABCB1 gene in osteosarcoma cells .These findings may provide a novel target for reversing doxorubicin resistance in OS.
Insights
A novel long non-coding RNA, ODRUL, is upregulated in osteosarcoma and promotes doxorubicin resistance by increasing ABCB1 expression. Inhibiting ODRUL may reverse resistance and reduce cancer cell proliferation and migration.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators in cancer development and progression.
- Aberrant lncRNA expression is implicated in osteosarcoma (OS), but their specific roles in doxorubicin resistance remain unclear.
- Understanding these mechanisms is crucial for improving chemotherapy efficacy in OS patients.
Purpose of the Study:
- To investigate the role of a novel lncRNA, ODRUL (osteosarcoma doxorubicin-resistance related up-regulated lncRNA), in doxorubicin resistance in OS.
- To elucidate the molecular mechanisms by which ODRUL influences chemoresistance and cancer cell behavior.
- To evaluate ODRUL as a potential therapeutic target for overcoming doxorubicin resistance in OS.
Main Methods:
- LncRNA microarray analysis to identify differentially expressed lncRNAs in doxorubicin-resistant OS cells.
- Quantitative real-time PCR (qRT-PCR) to validate ODRUL expression in OS cell lines and patient specimens.
- In vitro experiments involving ODRUL inhibition to assess its impact on OS cell proliferation, migration, and doxorubicin sensitivity.
- Analysis of ABCB1 gene expression following ODRUL knockdown.
Main Results:
- LncRNA ODRUL was significantly upregulated in doxorubicin-resistant OS cell lines and in OS patient specimens with poor chemoresponse and lung metastasis.
- Inhibition of ODRUL suppressed OS cell proliferation and migration in vitro.
- ODRUL knockdown partially reversed doxorubicin resistance in OS cells.
- Knockdown of ODRUL led to decreased expression of the ATP-binding cassette, subfamily B, member 1 (ABCB1) gene.
Conclusions:
- LncRNA ODRUL acts as a pro-doxorubicin-resistant factor in osteosarcoma by upregulating the expression of the ABCB1 gene.
- ODRUL inhibition demonstrates potential in reversing doxorubicin resistance and controlling tumor progression in OS.
- ODRUL represents a promising novel therapeutic target for overcoming chemoresistance in osteosarcoma.
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