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Study On Susceptibility Of MiRNA Gene Genetic Variation And Abnormal Tooth Number Development

Posted on:2021-12-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:M GuFull Text:PDF
GTID:1484306473468124Subject:Oral Medicine
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Objective: Non-syndromic supernumerary teeth(NSST)is a common type of dental anomaly.micro RNAs(miRNAs)play an important role in craniofacial and tooth development.This study aimed to investigate that single nucleotide polymorphisms(SNPs)of miRNAs may be associated with the susceptibility of NSST.Materials and methods: Four miRNA SNPs(rs2910164,rs11614913,rs2043556,and rs2682818)were selected,and their associations with NSST susceptibility were evaluated in a case-control study(163 NSST patients and 326 healthy controls).Results: rs2910164 was significantly associated with the risk of lower NSST(additive model: OR=4.00,95% CI=1.76-9.09,P=0.001)and rs2682818 showed nominal associations with the risk of upper NSST(additive model: OR=1.40,95%CI=1.02-1.91,P=0.037),and NSST among male patients(additive model: OR=1.62,95%CI=1.08-2.43,P=0.020).Conclusion: Genetic variants of miR-146a/rs2910164 and miR-618/rs2682818 were probably associated with the risk of NSST in the Chinese Han population.Objective: Non-syndromic tooth agenesis(NSTA)is one of the most common dental abnormalities in our daily clinical work.Mi RNAs participated in the craniofacial and tooth development.Therefore our study aimed to investigate single nucleotide polymorphisms(SNPs)in miRNA genes may contribute to the susceptibility of NSTA.Materials and methods: A total of 625 NSTA cases and 1,144 healthy controls were recruited,and four miRNA SNPs(miR-146a/rs2910164,miR-196a2/rs11614913,premiR-605/rs2043556,pre-miR-618/rs2682818)were genotyped by the Taq Man platform.Results: Rs2043556 showed nominal associations with NSTA risk(PAdd=0.021)in the overall analysis,as well as upper lateral incisor agenesis(PAdd=0.047)and lower incisor agenesis(PAdd=0.049)in the subgroup analysis.Notably,its significant association with upper canine agenesis was observed(PAdd=0.0016).Conclusion: Rs2043556 affected the mature of miR-605-3p and miR-605-5p while dual-luciferase report analysis indicated that MDM2 was the binding target of miR-605-5p.Our study indicated that pre-miR-605 rs2043556 was associated with risk of NSTA.Objective: There is a high incidence rate of malign parotid carcinoma in the head and neck tumor.Epigenetic alterations of DNA repair genes or cell cycle control genes are very frequent in sporadic(non-germ line)cancers,including parotid carcinoma.This study aimed to investigate the relationship between the expression of NSD2 in parotid carcinoma,and to explore the effect of down-regulating NSD2 gene expression on proliferation,apoptosis and invasion of parotid carcinoma.Materials and methods: SACC-2 cells were transfected with NSD2 siRNA.We use real-time quantitative PCR mean to detect the expression of NSD2 m RNA.And at the same time the expression of NSD2 protein was detected by western blot method.CCK-8 and colony formation test were used to detect cell proliferation.We detect apoptosis by Annexin V PI double staining flow cytometry,and also perform cell scratch test and transwell test to detect oral cell invasion.Results: For NSD2,the expression of si NSD2-1,si NSD2-2 and control were 0.238 ± 0.027,0.103 ± 0.017 and 1.129 ± 0.124(P < 0.05).For H3K36me2,the expression of si NSD2-1,si NSD2-2 and control were 0.122 ± 0.018,0.09 ± 0.021 and 1.201 ± 0.108,respectively(P < 0.05).The apoptosis rates of si NSD2-1 and si NSD2-2 groups were(21.77 ± 3.19)% and(29.84 ± 2.78)%.Meanwhile control group was(10.50 ± 2.14)%.The wounds of si NSD2-1 and si NSD2-2 group were more remarkable than control group.Relative migration distances were reduced remarkably than the control group(P < 0.05).The cells which penetrated cell membrane of si NSD2-1(24.34 ± 3.58)and si NSD2-2(24.34 ± 3.58)were significantly less than those of control(50.69 ± 9.57)(P < 0.05).Conclusion: Silencing NSD2 gene can inhibit the proliferation and invasion of parotid carcinoma SACC-2 cells and induce apoptosis.
Keywords/Search Tags:Non-syndromic supernumerary teeth, single nucleotide polymorphisms, miRNA, single nucleotide polymorphism, non-syndromic tooth agenesis, parotid carcinoma, NSD2, proliferation, invasion, apoptosis
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