miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis | |
Bai, Haitao ; Cao, Zhongwei ; Deng, Chong ; Deng C(邓聪) ; Zhou, Lili ; Wang, Chun | |
2012-04 | |
关键词 | Chemoresistance miR-181a Ara-C Acute myeloid leukaemia Bcl-2 |
英文摘要 | Ara-C is one of the most commonly used drugs in the treatment of AML. However, the development of drug resistance always prevented its further use. It has been shown that miR-181a is associated with the clinical outcome of AML patients. Here, we investigated the possible role of miR-181a in AML Ara-C resistance. miR-181a expression was measured by real-time PCR. Cell viability was detected by MTT assay. Protein expressions were measured by western blotting. Caspase activity was examined by florescence assay. We found that miR-181a expression was downregulated in the Ara-C-resistant cell line HL-60/Ara-C compared with its parental cell line HL-60. Overexpression of miR-181a in HL-60/Ara-C cells sensitized the cells to Ara-C treatment. Furthermore, Bcl-2 was confirmed as a direct miR-181a target by immunoblot analysis and reporter gene assays. Knockdown of Bcl-2 mimicked the effect of enforced miR-181a expression by reducing cell viability. In addition, the apoptosis pathway was activated by cytochrome C release and caspase 9/caspase 3 activation after miR-181a overexpression. This study for the first time demonstrated that downregulation of miR-181a and upregulation of Bcl-2 in leukaemia cells confer resistance to Ara-C-based therapy. These results suggest that restoration of miR-181a expression might provide a promising therapeutic in drug resistance of leukaemia.; Shanghai Jiaotong University Affiliated Shanghai First People's Hospital [061138] |
语种 | 英语 |
出版者 | SPRINGER |
内容类型 | 期刊论文 |
源URL | [http://dx.doi.org/10.1007/s00432-011-1137-3] |
专题 | 医学院-已发表论文 |
推荐引用方式 GB/T 7714 | Bai, Haitao,Cao, Zhongwei,Deng, Chong,et al. miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis[J],2012. |
APA | Bai, Haitao,Cao, Zhongwei,Deng, Chong,邓聪,Zhou, Lili,&Wang, Chun.(2012).miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis.. |
MLA | Bai, Haitao,et al."miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis".(2012). |
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