Nuclear Paraspeckle Assembly Transcript 1 Enhances Hydrogen Peroxide-Induced Human Vascular Smooth Muscle Cell Injury by Regulating miR-30d-5p/A Disintegrin and Metalloprotease 10

• Published in: Circulation Journal 2022/05/25, Vol.86(6), pp.1007-1018
• Main Authors: Zhou, Fushuo, Zheng, Zhi, Zha, Zhengbiao, Xiong, Tianxin, Pan, Youmin
• Format: Article
• Language: English
• Subjects: A disintegrin and metalloprotease 10 (ADAM10); Aneurysm; Apoptosis; Carrier Proteins; Cell Proliferation; Disintegrins - metabolism; Disintegrins - pharmacology; Humans; Hydrogen Peroxide - metabolism; Hydrogen Peroxide - pharmacology; Metalloproteases - metabolism; Metalloproteases - pharmacology; MicroRNAs - metabolism; miR-30d-5p; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - metabolism; Nuclear paraspeckle assembly transcript 1 (NEAT1); Paraspeckles; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism
• ISSN: 1346-9843; 1347-4820; 1347-4820
• DOI: 10.1253/circj.CJ-21-0042

Background: Nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to be involved in the progression of many cancers; however, the role and mechanisms underlying NEAT1 in abdominal aortic aneurysm (AAA) remain unclear.Methods and Results: The expression of NEAT1, miR-30d-5p and A disintegrin and metalloprotease 10 (ADAM10) was measured by qRT-PCR and western blot. Functional experiments were conducted by using a CCK-8 assay, EDU assay, flow cytometry, western blot, ELISA, and commercial kits. The target relation was confirmed by dual-luciferase reporter assay and the RIP assay. It was then found that NEAT1 was upregulated in peripheral blood of AAA patients ~3.46-fold, smooth muscle cells (SMCs) isolated from AAA tissues ~2.6-fold and in a hydrogen peroxide (H2O2)-induced injury model of human vascular SMC (HVSMCs) ~2.0- and 3.9-fold at 50 µmol/L and 200 µmol/L H2O2treatment, respectively. NEAT1 deletion attenuated H2O2-induced cell proliferation promotion (40.0% vs. 74.3%), apoptosis inhibition (25.0% vs. 13.5%), and reduction of inflammatory response and oxidative stress in HVSMCs. Mechanistically, NEAT1 targeted miR-30d-5p to prevent the degradation of its target, ADAM10, in HVSMCs. Further rescue experiments suggested miR-30d-5p inhibition mitigated the effects of NEAT1 deletion on H2O2-induced HVSMCs. Moreover, ADAM10 overexpression counteracted the inhibitory functions of miR-30d-5p on H2O2-evoked HVSMC injury.Conclusions: NEAT1 promoted H2O2-induced HVSMC injury by inducing cell apoptosis, inflammation and oxidative stress through miR-30d-5p/ADAM10 axis, indicating the possible involvement of NEAT1 in the pathogenesis of AAA.