Long non-coding RNA PVT1/microRNA miR-3127-5p/NCK-associated protein 1-like axis participates in the pathogenesis of abdominal aortic aneurysm by regulating vascular smooth muscle cells. Issue 2 (20th December 2021)

• Record Type: Journal Article
• Authors: Huang, Youjin; Ren, Li; Li, Jiajia; Zou, Haibo
• Is Part Of: Bioengineered. Volume 12:Issue 2(2021)
• Page Start: 12583
• Page End: 12596
• Publication Date: 2021-12-20
• Subjects: lncRNA PVT1 -- miR-3127-5p -- NCKAP1L -- abdominal aortic aneurysm; Biomedical engineering -- Periodicals; Biotechnology -- Periodicals; Microbiology -- Periodicals; 660.6
• DOI: 10.1080/21655979.2021.2010384
• Languages: English
• ISSNs: 2165-5987

Abstract

ABSTRACT: The long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) has been implicated in the progression of abdominal aortic aneurysms (AAA). However, the detailed mechanism requires further analysis. Our study was aimed at interrogating the mechanism of PVT1 in an H2 O2 -induced AAA model in vitro . The expression of lncRNA PVT1, microRNA miR-3127-5p, and NCK-associated protein 1-like (NCKAP1L) was examined in AAA tissues and H2 O2 -treated vascular smooth muscle cells (VSMCs). Cell proliferation was assayed using Cell Counting Kit-8 (CCK8) and 5-Bromodeoxyuridine (BrdU) assays. Meanwhile, 5-Ethynyl-2′-deoxyuridine (EdU) staining was performed to assess cell apoptosis and caspase-3 activity. IL-1β and caspase-1 expression was also assessed using Western blotting to determine inflammasome activation in H2 O2 -treated VSMCs. Luciferase reporter assays addressed the possible interaction between miR-3127-5p and PVT1 or NCKAP1L, which was predicted by starBase analysis. PVT1 and NCKAP1L expression was elevated in AAA tissues and induced the AAA model in vitro, whereas miR-3127-5p showed the opposite trend. Functionally, PVT1 silencing promoted cell proliferation and reduced the apoptotic rate and inflammasome activation in H2 O2 -treated VSMCs. Mechanical investigation demonstrated that PVT1 acted as a sponge of miR-3127-5p to modulate NCKAP1L expression, resulting in suppression of VSMC proliferation, induction of apoptosis, and activation of inflammation. In conclusion, PVT1 participates in AAA progression through the miR-3127-5p/NCKAP1L axis and may be a promising biosignature and therapeutic target for AAA.