Abstract |
Neuroblastoma (NB) is a common pediatric malignancy with high mortality in childhood. Although many attentions have been gained, novel biomarkers for NB diagnosis and prognosis are still needed. microRNAs ( miRNAs) played important roles in NB progression and miR-34a is a tumor suppressor in NB. However, the mechanism that underlies miR-34a regulating proliferation, migration, invasion and autophagy in NB remains poorly understood. In this study, cell proliferation was investigated by MTT and colony assay. Cell apoptosis was measured by caspase 3 activity assay. Cell migration and invasion were detected by trans-well analysis. Autophagy was measured via GFP-LC3 puncta fluorescence assay and western blots (WB). The expression of miR-34a was examined by quantitative real-time PCR (qRT-PCR). The regulatory effect of miR-34a on autophagy-related gene 5 (ATG5) was detected by qRT-PCR and WB. The interaction between miR-34a and ATG5 was probed by luciferase activity and RNA immunoprecipitation (RIP) assay. Results showed that miR-34a expression was inhibited in NB tissues and cells with low survival rate. Addition of miR-34a suppressed cell proliferation, migration, invasion and autophagy but promoted apoptosis in NB cells, whereas miR-34a deficiency played opposite roles in NB progression. Intriguingly, ATG5 was directly targeted by miR-34a. Moreover, ATG5 restoration attenuated miR-34a-mediated inhibitory effect on proliferation, apoptosis, migration, invasion and autophagy. These results indicated miR-34a suppressed proliferation, apoptosis, migration, invasion and autophagy in NB cells by targeting ATG5, providing a novel therapeutic avenue for NB treatment.
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Authors | Xinru Cheng, Qianya Xu, Yixia Zhang, Min Shen, Shanshan Zhang, Fengxia Mao, Bing Li, Xiaomin Yan, Zanyang Shi, Li Wang, Guangyao Sheng, Qian Zhang |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 850
Pg. 53-63
(May 05 2019)
ISSN: 1879-0712 [Electronic] Netherlands |
PMID | 30716314
(Publication Type: Journal Article)
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Copyright | Copyright © 2019 Elsevier B.V. All rights reserved. |
Chemical References |
- Autophagy-Related Protein 5
- MIRN34 microRNA, human
- MicroRNAs
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Topics |
- Apoptosis
(genetics)
- Autophagy
(genetics)
- Autophagy-Related Protein 5
(genetics)
- Base Sequence
- Cell Line, Tumor
- Cell Movement
(genetics)
- Cell Proliferation
(genetics)
- Disease Progression
- Female
- Humans
- Infant
- Male
- MicroRNAs
(genetics)
- Neoplasm Invasiveness
- Neuroblastoma
(genetics, pathology)
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