MiR-362-5p promotes the malignancy of chronic myelocytic leukaemia via down-regulation of GADD45α
| Autor: | Peng, Yang, Fang, Ni, Rui-Qing, Deng, Guo, Qiang, Hua, Zhao, Ming-Zhen, Yang, Xin-Yi, Wang, You-Zhi, Xu, Li, Chen, Dan-Lei, Chen, Zhi-Jun, Chen, Li-Xin, Kan, Si-Ying, Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Down-Regulation Mice Nude Apoptosis Cell Cycle Proteins Real-Time Polymerase Chain Reaction Mice Cell Movement Cell Line Tumor Leukemia Myelogenous Chronic BCR-ABL Positive Animals Humans CML Oncogene Cell Proliferation Mice Inbred BALB C Research Cell Cycle Nuclear Proteins P38 Gene Expression Regulation Neoplastic MicroRNAs HEK293 Cells Oncology Molecular Medicine GADD45α Female miR-362-5p K562 Cells JNK1/2 |
| Zdroj: | Molecular Cancer |
| ISSN: | 1476-4598 |
| Popis: | Background MicroRNAs (miR, miRNAs) play pivotal roles in numerous physiological and pathophysiological contexts. We investigated whether miR-362-5p act as an oncogene in chronic myeloid leukaemia (CML) and aimed to understand its potential underlying mechanisms. Methods We compared the miR-362-5p expression levels between CML and non-CML cell lines, and between fresh blood samples from CML patients and normal healthy controls using quantitative real-time PCR (qPCR). Cell counting kit-8 (CCK-8) and Annexin V-FITC/PI analyses were used to measure the effects of miR-362-5p on proliferation and apoptosis, and Transwell assays were used to evaluate migration and invasion. A xenograft model was used to examine in vivo tumourigenicity. The potential target of miR-362-5p was confirmed by a luciferase reporter assay, qPCR and western blotting. Involvement of the JNK1/2 and P38 pathways was investigated by western blotting. Results miR-362-5p was up-regulated in CML cell lines and fresh blood samples from CML patients, and was associated with Growth arrest and DNA damage-inducible (GADD)45α down-regulation. Inhibition of miR-362-5p simultaneously repressed tumour growth and up-regulated GADD45α expression in a xenograft model. Consistently, the knockdown of GADD45α expression partially neutralized the effects of miR-362-5p inhibition. Furthermore study suggested that GADD45α mediated downstream the effects of miR-362-5p, which might indirectly regulates the activation of the JNK1/2 and P38 signalling pathways. Conclusion miR-362-5p acts as an oncomiR that down-regulates GADD45α, which consequently activates the JNK1/2 and P38 signalling. This finding provides novel insights into CML leukaemogenesis and may help identify new diagnostic and therapeutic targets. Electronic supplementary material The online version of this article (doi:10.1186/s12943-015-0465-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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