MicroRNA-99a-5p alleviates atherosclerosis via regulating Homeobox A1.

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.

• 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)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• 3' Untranslated Regions
• Homeodomain Proteins
• MIRN99 microRNA, human
• MicroRNAs
• Transcription Factors
• homeobox A1 protein

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)