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 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 () mice.
Conclusions: This study demonstrated that TPRG1-AS1 inhibited HASMCs migration through interacting with MYH9 protein and consequently suppressed neointima formation and atherosclerosis.
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http://dx.doi.org/10.1161/ATVBAHA.122.318158 | DOI Listing |
Discov Oncol
December 2024
Department of Gynecology, The Second Affiliated Hospital of Xuzhou Medical University, No.99 West Huaihai Road, Quanshan District, Xuzhou, 221000, Jiangsu, China.
Objective: Cervical squamous cell carcinoma (CSCC) has a poor prognosis due to persistent HPV infection. LncRNA TPRG1-AS1 is linked to regulating the development of many cancers, so the regulatory mechanism and prognostic value of TPRG1-AS1 in CSCC were explored.
Methods: 138 patients with cervical cancer were included.
Anticancer Res
November 2024
Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea;
Background/aim: Certain long non-coding RNAs (lncRNAs), identified as potential tumor suppressors, have shown potential in inhibiting tumor growth. Here, we investigated a novel mechanism involving the direct interaction between lncRNA TPRG1-AS1 and Clathrin Heavy Chain (CLTC) in the Epidermal Growth Factor (EGF) signaling pathway for its tumor-suppressive effects.
Materials And Methods: Our research revealed a direct physical interaction between TPRG1-AS1 and CLTC through RNA pulldown and RNA immunoprecipitation (RIP)-qPCR, which subsequently influenced the EGF signaling pathway.
J Inflamm Res
November 2023
Department of Cardiology, Intervention Cardiology Center, Wuhan No.1 Hospital, Wuhan, 430022, People's Republic of China.
Purpose: Acute coronary syndrome (ACS) is a common acute myocardial ischemia syndrome and is one of the death-related causes of cardiovascular diseases. Identifying biomarkers to indicate disease severity and predict the occurrence of major adverse cardiovascular events (MACE) would benefit the clinical prognosis of ACS. This study estimated the expression and significance of lncRNA TPRG1-AS1 in the onset and development of ACS, aiming to explore a novel biomarker for the diagnosis and prognosis of ACS.
View Article and Find Full Text PDFSci Rep
July 2023
Department of Pharyngolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Head and neck squamous cell carcinoma (HNSC) is one of the leading causes of cancer death globally, yet there are few useful biomarkers for early identification and prognostic prediction. Previous studies have confirmed that CCND1 amplification is closely associated with head and neck oncogenesis, and the present study explored the ceRNA network associated with CCND1. Gene expression profiling of the Head and Neck Squamous Cell Carcinoma (HNSC) project of The Cancer Genome Atlas (TCGA) program identified the TPRG1-AS1-hsa-miR-363-3P-MYO1B gene regulatory axis associated with CCND1.
View Article and Find Full Text PDFCell Signal
February 2023
Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, PR China; Institute of Urology, China Medical University, Shenyang 110001, Liaoning, PR China. Electronic address:
Background: Overexpression of TFAP2A has been linked to increased lymph node metastasis in basal-squamous bladder cancer. However, its downstream targets in bladder urothelial carcinoma (BLCA), the most malignant cancer of the urinary tract, remain unclear. In the current study, we aim to explore the function and mechanism of TFAP2A in BLCA.
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