Abstract | AIMS:
MicroRNAs have been demonstrated to be involved in the development of atherosclerosis. The present study aimed to evaluate the effect of miR-99a-5p and its target gene Homeobox A1 (HOXA1) in atherosclerosis. MAIN METHODS: The biological functions of miR-99a-5p on human aortic smooth muscle cells (ASMCs) were assessed by MTT, wound healing and transwell assays. The target genes of microRNAs were predicted by TargetScan and miRDB. The binding of miR-99a-5p and HOXA1 was confirmed by luciferase reporter assay. In the in vivo study, high-fat diet-induced atherosclerosis model was established in Apolipoprotein E knockout mice. Hematoxylin- eosin (H&E), oil Red O and Masson trichrome staining were performed for determination of atherosclerotic lesion. The levels of miR-99a-5p and HOXA1 mRNA were detected by real-time PCR. HOXA1 and migration-associated protein levels were detected by western blot or immunohistochemistry analysis. KEY FINDINGS: MiR-99a-5p inhibited HOXA1 expression by targeting 3'UTR of HOXA1 mRNA. Enforced HOXA1 significantly promoted the proliferation, migration, and invasion of ASMCs. Furthermore, miR-99a-5p overexpression inhibited the proliferation, migration, and invasion of ASMCs stimulated by HOXA1, whereas miR-99a-5p inhibition reversed the effects of HOXA1 knockdown on these behaviours of ASMCs. In vivo, the specific overexpression of miR-99a-5p significantly abated atherosclerotic lesions formatted, accompanied with a significant down-regulation of HOXA1 mRNA and protein expression levels. SIGNIFICANCE: We demonstrate for first time that miR-99a-5p may serve as a potential inhibitor of the atherosclerosis, and miR-99a-5p plays its role partially through targeting HOXA1.
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Authors | Zhiyang Han, Yinghui Guan, Bing Liu, Yu Lin, Yan Yan, Haijun Wang, Hengzhen Wang, Bao Jing |
Journal | Life sciences
(Life Sci)
Vol. 232
Pg. 116664
(Sep 01 2019)
ISSN: 1879-0631 [Electronic] Netherlands |
PMID | 31325426
(Publication Type: Journal Article)
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Copyright | Copyright © 2019 Elsevier Inc. All rights reserved. |
Chemical References |
- 3' Untranslated Regions
- Homeodomain Proteins
- MIRN99 microRNA, human
- MicroRNAs
- Transcription Factors
- homeobox A1 protein
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Topics |
- 3' Untranslated Regions
- Animals
- Atherosclerosis
(genetics, prevention & control)
- Cell Movement
(physiology)
- Cell Proliferation
(physiology)
- Cells, Cultured
- Gene Expression Regulation
- Genes, Homeobox
- Homeodomain Proteins
(genetics, physiology)
- Humans
- Male
- Mice
- Mice, Knockout
- MicroRNAs
(physiology)
- Muscle, Smooth, Vascular
(cytology, metabolism)
- Transcription Factors
(genetics, physiology)
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