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Updated: Mar 31, 2026
Colony Formation Assay Detecting the Proliferative Capacity of LncRNA-knockdown Osteosarcoma Cells
Published on: January 16, 2026
Long noncoding RNA expression profiles of the doxorubicin-resistant human osteosarcoma cell line MG63/DXR and its
Kun-Peng Zhu1, Chun-Lin Zhang2, Guo-Qi Shen3
1Department of Orthopaedic Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University Shanghai 200233, PR China.
Abstract:
Long non-coding RNAs (lncRNAs) are emerging in molecular biology as crucial regulators of cancer. The efficacy of doxorubicin--based chemotherapy in osteosarcoma (OS) is usually limited by acquired drug resistance. To explore the mechanism of chemoresistance of OS in terms of lncRNA, using a human lncRNA-mRNA combined microarray, we identified 3,465 lncRNAs (1,761 up and 1,704 down) and 3,278 mRNAs (1,607 up and 1,671 down) aberrantly expressed in all three sets of doxorubicin-resistant MG63/DXR and their paired parental MG63 cells (fold-change >2.0, P<0.05 and FDR <0.05). Fifteen randomly selected lncRNAs were dysregulated in MG63/DXR cells relative to MG63 cells by qRT-PCR detection, which were consistent with our microarray data. Bioinformatics analysis identified that classical genes and pathways involved in cell proliferation, apoptosis, and drug metabolism were differently expressed in these cell lines. A lncRNA-mRNA co-expression network identified lncRNAs, including ENST00000563280 and NR-036444, may play a critical role in doxorubicin-resistance of OS by interacting with important genes such as ABCB1, HIF1A and FOXC2. Besides, we found that lncRNA ENST00000563280 was distinctly increased in specimens of OS patients with a poor chemoresponse compared to those with a good chemoresponse and the patients of lower expression of it may survive longer than those of higher expression, which suggest that it may serve as a biomarker to predict the chemoresponse and prognosis of osteosarcoma patients. These results provide important insights about the lncRNAs involved in osteosarcoma chemoresistance and lay a solid foundation for uncovering the mechanism ultimately.
Insights
Long non-coding RNAs (lncRNAs) regulate osteosarcoma (OS) chemoresistance. Specific lncRNAs like ENST00000563280 are linked to doxorubicin resistance and can predict patient outcomes, offering new therapeutic targets.
Area of Science:
- Molecular Biology
- Cancer Research
- Genomics
Background:
- Osteosarcoma (OS) chemotherapy efficacy is often limited by acquired drug resistance.
- Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators in cancer development and progression.
Purpose of the Study:
- To investigate the role of lncRNAs in doxorubicin chemoresistance in osteosarcoma.
- To identify specific lncRNAs and their associated genes involved in chemoresistance mechanisms.
Main Methods:
- Utilized a human lncRNA-mRNA combined microarray to analyze gene expression in doxorubicin-resistant MG63/DXR cells versus parental MG63 cells.
- Validated microarray findings using qRT-PCR for selected lncRNAs.
- Performed bioinformatics analysis and constructed a lncRNA-mRNA co-expression network.
Main Results:
- Identified 3,465 aberrantly expressed lncRNAs and 3,278 differentially expressed mRNAs in resistant cells.
- Discovered that lncRNAs ENST00000563280 and NR-036444 may critically influence doxorubicin resistance by interacting with genes like ABCB1, HIF1A, and FOXC2.
- Found elevated ENST00000563280 expression in OS patients with poor chemoresponse, suggesting its potential as a prognostic biomarker.
Conclusions:
- lncRNAs play a significant role in osteosarcoma chemoresistance.
- Specific lncRNAs, such as ENST00000563280, could serve as biomarkers for predicting chemoresponse and prognosis in OS patients.
- These findings provide a foundation for understanding lncRNA mechanisms in OS chemoresistance and developing targeted therapies.
