miR-124a Involves in the Regulation of Wnt/β-Catenin and P53 Pathways to Inhibit Abdominal Aortic Aneurysm via Targeting BRD4

BACKGROUND: Abdominal aortic aneurysm (AAA) belongs to a progressive, gradual aortic rupture, which can lead to death without surgical intervention. The key factors regulating the occurrence and progress of AAA are not clear. Increasing studies have indicated that microRNA (miRNA) plays an important role in cancer development. miR-124a serves as a tumor suppressor in several neoplasms, and its upregulation can greatly inhibit the life activities such as malignant growth and migration of tumor cells. AIM: The objective of this study is to explore the association of miR-124a with AAA and to uncover the regulated mechanism of miR-124a on AAA progression. METHODS: The specimens from the AAA patients were used for observing the miR-124a expression, and human aortic endothelial cells (hAoECs) were treated with AngII to establish the AAA cell models. The quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), CCK-8, transwell assay, flow cytometry assay, and western blot were conducted to unearth the regulation mechanism of miR-124a on AAA, and the dual-luciferase reporter assay was employed to investigate the downstream target of miR-124a. RESULTS: miR-124a was significantly downregulated in the whole blood of the patients, and the decreased miR-124a was also observed in AAA cell models. Overexpressing miR-124a could effectively inhibit the proliferation and migration and promote the apoptosis of the AAA cells. The dual-luciferase reporter assay confirmed that BRD4 was a downstream target of miR-124a, and BRD4 upregulation could obviously reverse the effects of miR-124a on the phenotype of AAA cells. Moreover, it was found that miR-124a could regulate the activities of Wnt/β-catenin and P53 pathways via targeting the BRD4. CONCLUSION: Our data suggested that miR-124a could regulate the activities of Wnt/β-catenin and P53 to suppress the AAA progression via targeting the BRD4.