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MicroRNA-21 regulates the sensitivity to cisplatin in a human osteosarcoma cell line
1Department of Orthopedics, Fifth Hospital of Wuhan, Hubei, 430050, People's Republic of China. sanming712@126.com.
Background:
Recent studies have shown that microRNA-21 (miR-21) is overexpressed in solid tumors and implicated in the modulation of drug-induced resistance.
Methods:
In this study, we investigated the anti-tumor effects of miR-21 on the sensitivity of osteosarcoma cells to CDDP.
Results:
Changes in the sensitivity of osteosarcoma cells to CDDP were examined after transfection with miR-21 mimics or anti-miR-21 or bcl-2 siRNA in combination with CDDP. Osteosarcoma cells transfected with miR-21 mimics were significantly resistant to CDDP, while suppression of miR-21 in osteosarcoma cells led to enhanced CDDP cytotoxicity. Moreover, the miR-21-induced changes in chemoresponse were ameliorated by down-regulation of bcl-2 by its siRNA.
Conclusion:
The miR-21 in osteosarcoma cells is a significant modulator of the anti-tumor effect of CDDP by regulating the expression of bcl-2, and the study reveals a novel mechanism of osteosarcoma drug resistance.
Insights
MicroRNA-21 (miR-21) overexpression in osteosarcoma increases resistance to CDDP chemotherapy. Suppressing miR-21 enhances CDDP
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNA-21 (miR-21) is frequently overexpressed in various solid tumors.
- miR-21 plays a role in modulating cellular resistance to chemotherapy-induced apoptosis.
Purpose of the Study:
- To investigate the role of miR-21 in osteosarcoma cell sensitivity to cisplatin (CDDP).
- To explore the underlying molecular mechanisms of miR-21-mediated chemoresistance.
Main Methods:
- Osteosarcoma cells were transfected with miR-21 mimics, anti-miR-21, or bcl-2 siRNA.
- Cellular sensitivity to CDDP was assessed following transfection and treatment.
- The expression of bcl-2 was evaluated in conjunction with miR-21 modulation.
Main Results:
- Overexpression of miR-21 in osteosarcoma cells conferred significant resistance to CDDP.
- Suppression of miR-21 expression enhanced the cytotoxic effects of CDDP.
- Down-regulation of bcl-2 using siRNA counteracted the chemoresistance induced by miR-21.
Conclusions:
- miR-21 acts as a key regulator of CDDP chemoresistance in osteosarcoma.
- The observed chemoresistance is mediated through the regulation of bcl-2 expression.
- This study elucidates a novel mechanism contributing to drug resistance in osteosarcoma.
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