Long Noncoding RNA TPRG1-AS1 Suppresses Migration of Vascular Smooth Muscle Cells and Attenuates Atherogenesis via Interacting With MYH9 Protein

Abstract

BACKGROUND: Migration of human aortic smooth muscle cells (HASMCs) contributes to the pathogenesis of atherosclerosis. This study aims to functionally characterize long noncoding RNA TPRG1-AS1 (tumor protein p63 regulated 1, antisense 1) in HASMCs and reveal the underlying mechanism of TPRG1-AS1 in HASMCs migration, neointima formation, and subsequent atherosclerosis. METHODS: The expression of TPRG1-AS1 in atherosclerotic plaques was verified a series of in silico analysis and quantitative real-time polymerase chain reaction analysis. Northern blot, rapid amplification of cDNA ends and Sanger sequencing were used to determine its full length. In vitro transcription-translation assay was used to investigate the protein-coding capacity of TPRG1-AS1. RNA fluorescent in situ hybridization was used to confirm its subcellular localization. Loss- and gain-of-function studies were used to investigate the function of TPRG1-AS1. Furthermore, the effect of TPRG1-AS1 on the pathological response was evaluated in carotid balloon injury model, wire injury model, and atherosclerosis model, respectively. RESULTS: TPRG1-AS1 was significantly increased in atherosclerotic plaques. TPRG1-AS1 did not encode any proteins and its full length was 1279nt, which was bona fide a long noncoding RNA. TPRG1-AS1 was mainly localized in cytoplasmic and perinuclear regions in HASMCs. TPRG1-AS1 directly interacted with MYH9 (myosin heavy chain 9) protein in HASMCs, promoted MYH9 protein degradation through the proteasome pathway, hindered F-actin stress fiber formation, and finally inhibited HASMCs migration. Vascular smooth muscle cell-specific transgenic overexpression of TPRG1-AS1 significantly reduced neointima formation, and attenuated atherosclerosis in apolipoprotein E knockout ( Apoe −/− ) mice. CONCLUSIONS: This study demonstrated that TPRG1-AS1 inhibited HASMCs migration through interacting with MYH9 protein and consequently suppressed neointima formation and atherosclerosis.

Exercise Mitigates Endothelial Pyroptosis and Atherosclerosis by Downregulating NEAT1 Through N6-Methyladenosine Modifications

“…24 Additionally, estrogen has an inhibitory effect on diet-induced atherosclerosis formation. [25][26][27] Therefore, to accelerate lesion formation, only male animals were used in our study. To establish atherosclerotic lesions, 6-to 8-week-old male ApoE −/− , ApoE −/− NEAT1 −/− , and ApoE −/− METTL14 +/− mice were fed a high-fat diet (HFD) containing 10% lard, 4% milk powder, 2% cholesterol, and 0.5% sodium cholate for 12 weeks.…”

DNAJA4 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma via PSMD2-mediated MYH9 degradation

“…MAP7D2 interacts with the MYH9 protein to protect it from ubiquitin-mediated degradation, subsequently reducing the secretion of HMGB1 to inhibit the infiltration of CD8 + cytotoxic T lymphocytes in microsatellite-stable colorectal cancer [ 54 ]. Conversely, the lncRNA TPRG1-AS1 directly interacts with MYH9 to promote its degradation through the proteasome pathway, subsequently hindering F-actin stress fiber formation and finally inhibiting the migration of human aortic smooth muscle cells [ 55 ]. In this study, we found that the proteasomal noncatalytic subunit PSMD2 interacted with MYH9 and induced its degradation via the ubiquitin-proteasome pathway in NPC.…”

Sleep Deprivation Promotes Endothelial Inflammation and Atherogenesis by Reducing Exosomal miR-182-5p

“…Relative protein levels were presented as percent lesion area: relative protein levels (%)=([positive protein in mm 2 /atherosclerotic lesion in mm 2 )×100). 33…”

“…Relative protein levels were presented as percent lesion area: relative protein levels (%)=([positive protein in mm 2 /atherosclerotic lesion in mm 2 )×100). 33 Masson staining was performed using a Modified Masson's Trichrome Stain Kit (Solarbio, China), and the mean area of the 6 sections/mouse was used for comparing among groups.…”