MicroRNA-370-3p inhibits human vascular smooth muscle cell proliferation via targeting KDR/AKT signaling pathway in cerebral aneurysm

W.-Z. Hou, X.-L. Chen, W. Wu, C.-H. Hang

Department of Neurosurgery, Jinling Hospital, School of Medicine, Southern Medical University (Guangzhou), Nanjing, Jiangsu Province, China. ChunhuaHang110@126.com

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• Neurology

OBJECTIVE: Cerebral aneurysm is a common vascular disease with high morbidity and mortality. Vascular smooth muscle deletion or dysplasia is an important reason for the development of cerebral aneurysm. MiRNAs participate in a variety of biological functions through inhibiting target gene translation. The aim of the present study was to evaluate the role of miRNAs in the regulation of vascular smooth muscle cell proliferation.

MATERIALS AND METHODS: MiRNA and mRNA expressions were tested by Real-time PCR. Cell cycle was detected by flow cytometry. Cell viability was evaluated by MTT assay. HUASMC cell proliferation was determined by BrdU assay. Protein expressions were determined using Western blot. MiRNA target gene was confirmed by luciferase assay.

RESULTS: MiR-370-3p expression was increased in cerebral aneurysm tissues. Ectopic expression of miR-370-3p suppressed proliferation of vascular smooth muscle cells and blocked cell cycle. Numerous cell proliferation and apoptosis-related factors were down-regulated by miR-370-3p. Results of target prediction database and dual-luciferase assay revealed that KDR is a direct target of miR-370-3p. Importantly, FOXO1 activity and AKT and FOXO1 phosphorylation were inhibited by miR-370-3p. We suggest that miR-370-3p directly targets KDR, resulting in the activation of AKT signaling pathway.

CONCLUSIONS: MiR-370-3p was involved in the development of cerebral aneurysm by targeting KDR and blocking AKT/FOXO1 signaling pathway. The results provide theoretical basis for further investigation of potential clinical prevention and treatment of cerebral aneurysm.

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