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MicroRNA-584 Impairs Cellular Proliferation and Sensitizes Osteosarcoma Cells to Cisplatin and Taxanes by Targeting
Li Li1,2, Xiang'an Kong2, Mousheng Zang2
1Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
Background:
Osteosarcoma (OS), an aggressive malignant neoplasm, exhibits osteoblastic differentiation. Cisplatin (DDP) and taxanes are among the most effective drugs for OS patients. Nevertheless, the drug resistance remains a main limitation to efficacious chemotherapy in OS. The current report sets to explore the biological function of microRNA-584 (miR-584) and the potential mechanism underlying OS cells resistance to these two drugs.
Materials And Methods:
The expression profiles of miR-584 and connective tissue growth factor (CTGF, CCN2) in OS tissue samples and cell lines were tested by means of reverse transcription-quantitative polymerase chain reaction and Western blot. U2OS and MG63 cell lines were delivered with miR-584 mimic alone or plus CCN2 to excavate theirs functions by cell counting kit-8 and EdU, flow cytometric analysis, as well as transwell assay, severally. Western bot analysis was conducted to examine the expression of IκBα, pIκBα, NF-κB and pNF-κB. Dual-luciferase reporter gene assay was carried out to assess the targets of miR-584.
Results:
The downregulation of miR-584 was identified in OS tissues and cells, which was closely linked to the dismal prognosis of OS patients. Overexpression of miR-584 repressed cell viability, migration as well as invasion, potentiated apoptosis and sensitized OS cells to DDP and taxanes. Mechanism investigation specified a direct targeting relationship between CCN2 and miR-584 in OS.
Conclusion:
In conclusion, miR-584 has the potency to act as a therapeutic maneuver for OS mainly by inducing the chemosensitivity of OS cells to DDP and taxanes.
Insights
MicroRNA-584 (miR-584) is downregulated in osteosarcoma (OS) and can overcome drug resistance. Restoring miR-584 enhances chemosensitivity to cisplatin and taxanes in OS cells.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is an aggressive cancer with limited chemotherapy options due to drug resistance.
- Cisplatin (DDP) and taxanes are key treatments, but resistance hinders efficacy.
- Understanding resistance mechanisms is crucial for improving OS treatment outcomes.
Purpose of the Study:
- To investigate the role of microRNA-584 (miR-584) in osteosarcoma (OS).
- To explore the underlying mechanisms of OS cell resistance to DDP and taxanes.
- To assess miR-584's potential as a therapeutic target for OS.
Main Methods:
- Quantitative reverse transcription PCR and Western blot analyzed miR-584 and CTGF (CCN2) expression in OS tissues and cell lines.
- Cell counting kit-8, EdU, flow cytometry, and transwell assays evaluated miR-584 and CCN2 functions.
- Western blot assessed NF-κB pathway proteins; dual-luciferase reporter assays identified miR-584 targets.
Main Results:
- miR-584 was downregulated in OS tissues and linked to poor prognosis.
- miR-584 overexpression reduced OS cell viability, migration, and invasion, while increasing apoptosis.
- miR-584 sensitized OS cells to DDP and taxanes, with CCN2 identified as a direct target.
Conclusions:
- miR-584 functions as a tumor suppressor in osteosarcoma.
- Restoring miR-584 can overcome chemoresistance in OS.
- miR-584 represents a potential therapeutic strategy to enhance chemosensitivity in OS patients.
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