Abstract
Thoracic aortic aneurysm (TAA) is a prevalent health problem worldwide. Long non-coding RNA H19was highly expressed in TAA patients, but the function and mechanism of H19 in TAA remain unknown. The expression levels of H19, microRNA-1-3p (miR-1-3p), and a disintegrin and metalloproteinase 10 (ADAM10) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROS) cure was performed to evaluate the diagnostic value of H19 on TAA patients. Proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry. Protein levels of proliferating cell nuclear antigen (PCNA), Cleaved-caspase 3 (Cleaved-cas3), Cleaved-caspase 9 (Cleaved-cas9), Collagen I, Collagen III, and ADAM10 were tested by western blot assay. The binding relationship between miR-1-3p and H19 or ADAM10 was predicted by LncBase Predicted v.2 or Starbase, and verified by the dual-luciferase reporter, RNA pull-down assay, and RNA Immunoprecipitation (RIP) assays. H19 was increased in TAA aorta tissues and serum and vascular smooth muscle cell (VSMC), and hindered proliferation as well as promoted apoptosis and extracellular matrix (ECM) degradation of VSMC. Moreover, miR-1-3p was decreased, and ADAM10 was upregulated in TAA aorta tissues and VSMC. The mechanical analysis confirmed that H19 affected ADAM10 expression by targeting miR-1-3p. Our results indicated that H19 inhibited proliferation, and accelerated apoptosis and ECM degradation of VSMC, providing an underlying lncRNA-targeted therapy for TAA treatment.
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Abbreviations
- TAA:
-
Thoracic aortic aneurysm
- RT-qPCR:
-
Real-time quantitative polymerase chain reaction
- ROS:
-
Receiver operating characteristic
- CCK-8:
-
Cell Counting Kit-8
- PCNA:
-
Proliferating cell nuclear antigen
- VSMC:
-
Vascular smooth muscle cell
- ECM:
-
Extracellular matrix
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This Work Support by Sanming Project of Medicine in Shenzhen (No. SZSM201811096).
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ZF participated in the design of the work, methodology, data interpretation, and analysis for the work, carried out the statistical analysis and drafted the manuscript. SL participated in the methodology, data interpretation, and analysis for the work. HZ designed the study, participated in data interpretation and methodology. All authors read and approved the final manuscript.
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Fan, Z., Liu, S. & Zhou, H. LncRNA H19 Regulates Proliferation, Apoptosis and ECM Degradation of Aortic Smooth Muscle Cells Via miR-1-3p/ADAM10 Axis in Thoracic Aortic Aneurysm. Biochem Genet 60, 790–806 (2022). https://doi.org/10.1007/s10528-021-10118-y
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DOI: https://doi.org/10.1007/s10528-021-10118-y