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Based On Bioinformatics Analysis Lncrna SNHG5 Changing The Function Of Vascular Smooth Muscle Cells Through Mir-205-5p/SMAD4 In Abdominal Aortic Aneurysm

Posted on:2022-10-11Degree:MasterType:Thesis
Country:ChinaCandidate:H NieFull Text:PDF
GTID:2480306506974709Subject:Surgery
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BackgroundAbdominal aortic aneurysm(AAA)is a disease in which the abdominal aorta gradually expands like a tumor under the influence of blood pressure.Generally,when the diameter of the abdominal aorta exceeds 3 cm or increases by more than50% compared with normal people,AAA can be diagnosed.AAA usually occurs in elderly men over 65,and its incidence can reach 8%.Because blood vessels cannot withstand the pressure of blood flow on them,the most serious consequence is the rupture of the arterial wall.The mortality of aneurysm rupture can exceed 80% and the mortality of patients with ruptured aneurysm undergoing repair surgery is still more than 50%.So far,no effective pharmacological therapy for clinical AAA management has been found,and endovascular repair or open surgery is still the only option to prevent aneurysm rupture.Non-coding RNA(nc RNA)is a transcript that is not translated into protein.In the past two decades,nc RNA has undergone tremendous changes.Originally regarded as "junk",it is now regarded as an important regulator of physiological and pathological processes.This study aims to analyze the gene sequencing chips of samples from AAA patients,construct a ceRNA network that plays an important role in AAA,and identify important nc RNAs that affect the occurrence and development of AAA.ObjectiveTo analyze the profiles of long non-coding RNA(lnc RNA)-messenger RNA(m RNA)co-expression network in patient and explore potential roles of the key lnc RNA SNHG5 changing the function of vascular smooth muscle cells in the abdominal aortic aneurysm(AAA).MethodsThe human gene expression profile GSE57691,was downloaded from the GEOdatabase.The microarray included gene expression array data of 49 abdominal aortic aneurysm patients and 10 control aortic specimens from organ donors.To determine their main roles in the biological network,we analyzed the differentially expressed LncRNA and m RNAs in the aortic aneurysm(AAA)and normal aortic specimens,constructed a ceRNA network using Cytoscape software,and analyzed five key LncRNA.We chose SNHG5,which was significantly down-regulated in the abdominal aortic aneurysm,and found that it regulates mir-205-5p and SMAD4 via mir-205-5p.Double luciferase reporter gene analysis,RNA immunoprecipitation(RIP),and RNA pull-down analysis were used to establish the relationship between SNHG5 and mir-205-5p.Apoptosis was detected using flow cytometry,cell proliferation was evaluated using Edu,and 24 well Transwell insert,and Western blot analysis was used to detect the protein expression.ResultsThe five LncRNA were highly correlated with 34 mi RNAs and 112 m RNA.m RNAs in the ceRNA network participate in protein binding,signal transduction,DNA,RNA transcription,development,and cell differentiation.SNHG5 was down-regulated in the abdominal aortic aneurysm and can be used as a molecular sponge of mir-205.Downregulation of SNHG5 can increase the mir-205-5p expression.The increased mir-205-5p can inhibit SMAD4 production,thus inhibiting the proliferation and migration of smooth muscle cells and promoting apoptosis.ConclusionWe use bioinformatics approaches to discuss the molecular mechanism of AAA production.Our study shows that lnc RNA SNHG5 can regulate the proliferation and apoptosis of VSMC cells via the mir-205-5p /SMAD4 axis.SNHG5 is an essential new SMC biology regulator and a potential therapeutic target for AAA diseases.
Keywords/Search Tags:abdominal aortic aneurysm, bioinformatics, vascular, LncRNA, ceRNA
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