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Journal of Cancer Research and Clinical Oncology

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01.04.2012 | Original Article

miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis

verfasst von: Haitao Bai, Zhongwei Cao, Chong Deng, Lili Zhou, Chun Wang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 4/2012

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Titel: miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis
verfasst von: Haitao Bai
Zhongwei Cao
Chong Deng
Lili Zhou
Chun Wang
Publikationsdatum: 01.04.2012
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 4/2012
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-011-1137-3

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miR-181a sensitizes resistant leukaemia HL-60/Ara-C cells to Ara-C by inducing apoptosis

Abstract

Background

Methods

Results

Conclusions

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Springer Medizin

Abstract

Background

Methods

Results

Conclusions

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