XIST knockdown suppresses vascular smooth muscle cell proliferation and induces apoptosis by regulating miR-1264/WNT5A/β-catenin signaling in aneurysm.

Liang Zou,Peng-Fei Xia,Lei Chen,Yan-Yan Hou

doi:10.1042/bsr20201810

Abstract

Long non-coding RNAs (lncRNAs) have been ascertained as vital modulators in abdominal aortic aneurysm (AAA) development. In this research, the function and molecular mechanisms of the lncRNA X-inactive specific transcript (XIST) in the evolution of vascular smooth muscle cells (VSMCs) were assessed. Results showed that XIST expression was increased but miR-1264 expression level was reduced in the serum of AAA patients. XIST depletion impeded human aorta VSMCs (HA-VSMCs’) ability to proliferate and stimulate apoptosis, while repressing miR-1264 expression through an unmediated interaction. Additionally, the influence of XIST knockdown on apoptosis and proliferation could be rescued by an miR-1264 inhibitor. Subsequent molecular investigations indicated that WNT5A was miR-1264’s target, and XIST functioned as a competing endogenous RNA (ceRNA) of miR-1264 to raise WNT5A expression. Further, an miR-1264 inhibitor stimulated the proliferation and suppressed the apoptosis of HA-VSMCs through the activation of WNT/β-catenin signaling. Taken together, XIST impeded the apoptosis and stimulated the proliferation of HA-VSMCs via the WNT/β-catenin signaling pathway through miR-1264, demonstrating XIST’s underlying role in AAA.

Highlights

Abdominal aortic aneurysm (AAA) is a cardiovascular disease triggering fatal rupture [1,2] and a significant cause of death in the elderly [3]
X-inactive specific transcript (XIST) and miR-1264 expression levels were first explored in the serum of AAA patients. qRT-Polymerase chain reaction (PCR) assay findings uncovered that XIST expression was increased (Figure 1A) while miR-1264 expression was pronouncedly reduced (Figure 1B) in the serum of AAA patients (n=24) relative to that of healthy volunteers (n=24)
Bioinformatics analysis was utilized to confirm the underlying miRNA targets for XIST to probe at the molecular mechanisms by which XIST regulates the development of human aorta vascular smooth muscle cell (VSMC) (HA-VSMC)

Summary

Introduction

Abdominal aortic aneurysm (AAA) is a cardiovascular disease triggering fatal rupture [1,2] and a significant cause of death in the elderly [3]. The disease manifests no symptoms prior to rupture, rupture in AAA cases often leads to death, with a mortality rate of 85–90% [10]. SMC apoptosis is an important pathological feature that leads to various mechanisms that modulate AAA [9]. Emphasis has been placed on the underlying mechanisms of SMC apoptosis for its contribution to the diagnosis and treatment of AAA. Many recent studies have indicated that various proteins can be used as biomarkers and therapeutic targets in AAA diagnosis and treatment due to their regulation of SMC apoptosis [11,12,13]

Methods

Results

Conclusion