miR-181a是否能调节白血病耐药细胞株K562/A02对道诺霉素(又称柔红霉素，daunorubicin)的敏感性，以及这种调节作用的内在机制如何？本研究发现白血病耐药细胞株K562/A02中的miR-181a水平要比白血病细胞株K562中的低。 同时K562转染了miR-181a抑制剂后细胞存活率上升；而K562/A02转染miR-181a类似物之后细胞存活率下降。而且miR-181a可以增强道诺霉素诱导的K562/A02细胞凋亡；而转染了BCL-2 siRNA的K562/A02细胞存活率下降。由此可见，miR-181a在K562/A02细胞的道诺霉素耐药性发展中起到一定的作用，而这种作用可能是通过BCL-2介导实现的。

图例: 白血病细胞株K562及其耐药株K562/02中miR-181a 和BCL2的相关性

miR-181a sensitizes a multidrug-resistant leukemia cell line K562/A02 to daunorubicin by targeting BCL-2

Hao Li, Lulu Hui, and Wenlin Xu

Department of Central Laboratory, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China.

The aim of this study was to investigate whether miR-181a could modulate the sensitivity of the leukemia drug-resistant cell line K562/A02 to the chemotherapeutic agent daunorubicin (DNR), and explore the mechanism of miR-181a on the DNR sensitivity of K562/A02 cells. MicroRNA microarray and stem-loop reverse transcription-polymerase chain reaction were used to detect the expression of miR-181a. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay was performed to quantify the effect of miR-181a on K562 cells growth and viability. Apoptotic cells were quantitatively detected using Annexin V/FITC and PI apoptosis detection kit. BCL-2 protein expression was measured by western blot. Luciferase reporter vector with the putative BCL-2 3' untranslated region was constructed to explore whether BCL-2 was a direct target gene of miR-181a. BCL-2 siRNA was transfected into the cell to explore the relationship between BCL-2 and DNR resistance. The miR-181a expression level was lower in the K562/A02 cells than in the K562 cells (P< 0.05). K562 cells that were transfected with miR-181a inhibitor had a significantly higher survival than K562 cells, and K562/A02 cells that were transfected with the miR-181a mimic had a significantly lower survival than K562/A02 cells (P< 0.05). miR-181a could enhance DNR-induced apoptosis in K562/A02 cells. BCL-2 siRNA transfected K562/A02 cells had decreased survival compared with the K562/A02 control group. In conclusion, miR-181a could play a role in the development of DNR resistance in K562/A02 cells and the over-expression of miR-181a could sensitize K562/A02 cells to DNR by targeting BCL-2.

Acta Biochim Biophys Sin (Shanghai). 2012 Mar;44(3):269-77. doi: 10.1093/abbs/gmr128.

全文：http://abbs.oxfordjournals.org/content/44/3/269.full.pdf+html