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MiR-20a-5p suppresses tumor proliferation by targeting autophagy-related gene 7 in neuroblastoma.

Abstract：

Background:Neuroblastoma (NB) is the most common malignant tumor originating from the extracranial sympathetic nervous system in children. The molecular mechanisms underlying this disease are complex, and not completely understood. Methods:Quantitative real-time PCR (qRT-PCR) was applied to quantify the expression of miR-20a-5p and its target gene ATG7 in clinical NB tissues. The biological function of miR-20a-5p and ATG7 in SH-SY5Y cells was investigated through in vitro studies (Real-Time cell kinetic analyzer, colony formation assay, caspase-Glo 3/7 assay and western blotting). The luciferase reporter assay was conducted to verify the biological relationship between miR-20a-5p and ATG7. Results:Here we found that miR-20a-5p expression was significantly downregulated whereas its target autophagy-related gene 7 (ATG7) was increased along with clinical staging of NB progression. Correlation analysis showed that miR-20a-5p had a negative correlation trend with ATG7. In SH-SY5Y cells, forced expression of miR-20a-5p suppressed ATG7 expression, autophagy initiation and cellular proliferation while promoted apoptosis, suggesting a potential association between miR-20a-5p and ATG7. Further bioinformatic target prediction combined with protein expression and luciferase reporter assay verified that miR-20a-5p inhibited ATG7 by directly binding to its 3'-UTR, confirming the involvement of miR-20a-5p in the regulation of ATG7 in NB. Conclusions:These results clarified that miR-20a-5p inhibited cell proliferation and promoted apoptosis through negative regulation of ATG7 and thus autophagy suppression in SH-SY5Y cells. Therefore, defining the context-specific roles of autophagy in NB and regulatory mechanisms involved will be critical for developing autophagy-targeted therapeutics against NB. Both miR-20a-5p and ATG7 would be potential therapeutic targets for future NB treatment.

journal_name

Cancer Cell Int

journal_title

Cancer cell international

authors

Yu Y,Zhang J,Jin Y,Yang Y,Shi J,Chen F,Han S,Chu P,Lu J,Wang H,Guo Y,Ni X

doi

10.1186/s12935-017-0499-2

subject

Has Abstract

pub_date

2018-01-04 00:00:00

pages

5

issn

1475-2867

pii

499

journal_volume

18

pub_type

杂志文章

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