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Inhibiting effects of arsenic trioxide in combination with miR-203 on leukemic K562 cells and its mechanisms
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Abstract:
Objective: To study the anti-tumor effect of arsenic trioxide (As 2O 3) in combination with overexpression of miR-203 on leukemic K562 cells. Methods: Eukaryotic expression vector of miR-203 (pmiR-203) was transfected into K562 cells. Transcript levels of miR-203 were quantified by real-time quantitative PCR. K562 cells were incubated with different concentrations of As 2O 3 alone or in combination with pmiR-203. Cell viability was measured by MTT assay. Cell apoptosis was analyzed using flow cytometry. Bcr/abl protein contents were assessed by Western blotting. The ability of miR-203 to bind to Bcr/abl 3′UTR was determined by Bcr/abl 3′UTR and Bcr/abl mut-3′UTR dual luciferase report vector assays. Results: Levels of miR-203 transcript were significantly increased in pmiR-203-transfected K562 cells. Overexpression of miR-203 combined with As 2O 3 treatment increased the sensitivity K562 cells to As 2O 3 by up to 4.86-fold alone while the IC 50 was decreased from 3.4 μmol/L to 0.7 μmol/L as compared with As 2O 3. The number of apoptotic cells was increased in pmiR-203-transfected K562 cells treated with As 2O 3 (\[29.97±3.19\]%) compared with As 2O 3 alone (\[10.77±1.71\]%,P <0.05). Overexpression of miR-203 resulted in decreases in Bcr/abl protein levels and Bcr/abl-3′UTR reporter activity without affecting activity of Bcr/abl-mut-3′UTR reporter in K562 cells. A binding site in the sequence of Bcr/abl-mut-3′UTR was identified. Conclusion: Overexpression of miR-203 may enhance the sensitivity of leukemic K562 cells to As 2O 3, at least partially through down-regulation of Bcr/abl expression.
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Project Supported:
Project supported by the Natural Science Foundation of Guangxi Zhuang Autonomous Region (No. 2012GXNSFAA053177)
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