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Published on: May 21, 2019
Downregulating long non-coding RNA PVT1 expression inhibited the viability, migration and phenotypic switch of
Shouming Li1, Xin Zhao2, Shaopeng Cheng1
1Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, No.107, West Wenhua Road, Jinan, 250012, Shandong, China.
Abstract:
Long non-coding RNA Plasmacytoma Variant Translocation 1 (LncRNA PVT1) was involved in various human diseases, but its role in aortic dissection (AD) remained to be fully examined. In this study, the viability and migration of human aortic smooth muscle cells (HASMCs) were respectively measured by MTT assay and wound-healing assay. Relative phenotypic switch-related protein expressions were measured with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. An AD model was established in animals and hematoxylin-eosin (H&E) staining was used for pathological examination. We found that, in HASMCs, microRNA (miR)-27b-3p could competitively bind with PVT1. In AD, PVT1 expression was upregulated, yet that of miR-27b-3p was downregulated. Downregulating PVT1 reversed the effects of growth factor-BB (PDGF-BB) treatment on PVT1, miR-27b-3p and expressions of phenotypic switch-related markers, and cell viability and migration, while downregulating miR-27b-3p reversed the effects of downregulating PVT1. Moreover, downregulating PVT1 suppressed the effects of upregulated PVT1 and downregulated miR-27b-3p induced by AD as well as media degeneration in vivo. In conclusion, downregulating PVT1 expression suppressed the proliferation, migration and phenotypic switch of HASMCs treated by PDGF-BB via targeting miR-27b-3p.
Insights
Long non-coding RNA PVT1 (Plasmacytoma Variant Translocation 1) down-regulation inhibits proliferation and migration in human aortic smooth muscle cells. This suggests PVT1 may be a therapeutic target for aortic dissection by modulating miR-27b-3p.
Area of Science:
- Molecular Biology
- Cardiovascular Biology
- Genetics
Background:
- Long non-coding RNA PVT1 (Plasmacytoma Variant Translocation 1) is implicated in various diseases.
- The specific role of PVT1 in aortic dissection (AD) requires further investigation.
- Understanding PVT1's function in human aortic smooth muscle cells (HASMCs) is crucial for AD research.
Purpose of the Study:
- To investigate the role of LncRNA PVT1 in the pathogenesis of aortic dissection (AD).
- To explore the interaction between PVT1 and microRNA-27b-3p (miR-27b-3p) in HASMCs.
- To determine the therapeutic potential of targeting PVT1 in AD.
Main Methods:
- Cell viability and migration assays (MTT, wound-healing) in HASMCs.
- Quantitative real-time PCR (qRT-PCR) and Western blot for gene and protein expression analysis.
- Establishment of an animal model for AD with pathological examination (H&E staining).
Main Results:
- PVT1 expression was upregulated, while miR-27b-3p was downregulated in AD.
- PVT1 competitively binds with miR-27b-3p in HASMCs.
- Downregulating PVT1 reversed PDGF-BB-induced changes in HASMCs and suppressed AD-induced pathology in vivo.
Conclusions:
- Downregulating PVT1 suppresses proliferation, migration, and phenotypic switching of HASMCs.
- PVT1 targets miR-27b-3p to influence HASMC behavior in the context of AD.
- PVT1 inhibition represents a potential therapeutic strategy for aortic dissection.
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