hsa-miR-203 enhances the sensitivity of leukemia cells to arsenic trioxide

He,Jin-Hua; Li,Yu-Min; Li,Yu-Guang; Xie,Xing-Yi; Wang,Li; Chun,Shun-Yi; Cheng,Wu-Jia

doi:10.3892/etm.2013.981

May 2013 Volume 5 Issue 5

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May 2013 Volume 5 Issue 5

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Article

hsa-miR-203 enhances the sensitivity of leukemia cells to arsenic trioxide

Authors:
- Jin-Hua He
- Yu-Min Li
- Yu-Guang Li
- Xing-Yi Xie
- Li Wang
- Shun-Yi Chun
- Wu-Jia Cheng
View Affiliations / Copyright

Affiliations: Department of Laboratory, Central Hospital of Panyu District, Guangzhou, Guangdong 511400, P.R. China, Department of Clinical Laboratory, Minzu Hospital, Nanning, Guangxi 530001, P.R. China
Pages: 1315-1321
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Published online on: February 27, 2013

https://doi.org/10.3892/etm.2013.981
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Abstract

The aim of this study was to investigate the effect of a eukaryotic expression vector expressing hsa-miR‑203 on the sensitivity of K562 leukemia cells to arsenic trioxide (ATO) and the possible mechanism of action. The eukaryotic expression vector expressing the hsa-miR‑203 plasmid (PmiR-203) was transfected into K562 cells using Lipofectamine 2000. bcr/abl 3' untranslated region (UTR) and bcr/abl mutated 3'UTR dual luciferase report vectors (psi-CHECK-2) were used to validate the regulation of bcr/abl by miR-203. The inhibitory effects of ATO and PmiR-203, used singly or in combination, on cell proliferation were detected by MTT assay. Apoptosis of the K562 cells was detected by ﬂow cytometry using double-staining with Annexin V and propidium iodide (PI). The activities of caspase-3 and caspase-9 were detected by a colorimetric method and the cytochrome c protein levels were detected by western blotting. When used in combination with PmiR-203, the IC50 of ATO was reduced from 6.49 to 2.45 µg/ml and the sensitivity of cells to ATO increased 2.64‑fold. In addition, PmiR-203 and ATO caused growth inhibition, apoptosis and G1-phase arrest in K562 cells. Furthermore, PmiR-203 signiﬁcantly promoted ATO-mediated growth inhibition and apoptosis, affecting the G1 phase. JC-1 fluorescent staining revealed that the membrane potential of the mitochondria had changed. The activities of caspase-3 and caspase-9 increased, the expression levels of cytochrome c were upregulated and the expression level of bcr/abl mRNA was significantly suppressed. Furthermore, the dual-luciferase reporter vector, containing tandem miR-203 binding sites from the bcr/abl 3'UTR, demonstrated that bcr/abl was directly regulated by miR-203. PmiR-203 sensitized K562 leukemia cells to ATO by inducing apoptosis and downregulating bcr/abl gene levels. The induction of apoptosis may occur through the mitochondrial pathway. The combination of ATO and PmiR‑203 presents therapeutic potential for chronic myelogenous leukemia.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

hsa-miR-203 enhances the sensitivity of leukemia cells to arsenic trioxide

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