WTAP-mediated m6A modification on BASP1 mRNA contributes to ferroptosis in AAA

Abstract

Background: Abdominal aortic aneurysm (AAA) is a common aneurysm that is often associated with atherosclerosis and can lead to artery rupture and death. Brain abundant membrane attached signal protein 1 (BASP1) is related to a variety of pathophysiological processes, but its role in AAA has not been reported.

Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) and western blot were used to detect the expressions of BASP1 and Wilms' tumor 1-associated protein (WTAP). Angiotensin-II (Ang-II) was employed for inducing AAA models in vitro to explore the effects and mechanism of BASP1 in AAA. Cell viability, apoptosis, oxidative stress level, and Fe²⁺ level were measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometry, and various kits, respectively. In terms of mechanism, the methylated RNA immunoprecipitation (MeRIP)-qPCR, the dual luciferase reporter assay, and the cytochrome experiments were utilized to evaluate the relationship between BASP1 and WTAP.

Results: A highly expressed level of BASP1 was observed in aortic tissues of AAA patients and Ang-II could induce AAA models by treating vascular smooth muscle cells (VSMCs). In cellular function, BASP1 knockdown impaired AAA and ferroptosis resulted from Ang-II. Mechanically, WTAP mediated the N6-methyladenosine (m6A) modification and mRNA stability of BASP1. Meanwhile, WTAP was highly expressed in AAA tissues of patients and the effects of WTAP silence in AAA and ferroptosis were diminished by up-regulated BASP1.

Conclusion: WTAP promotes cell viability and inhibits apoptosis and ferroptosis resulted from Ang-II in VSMCs by mediating the m6A level of BASP1.

Keywords: N 6-methyladenosine; Abdominal aortic aneurysm; Brain abundant membrane attached signal protein 1; Ferroptosis; Wilms’ tumor 1-associated protein.