[1]张艳梅,马靖华,刘阳晨,等.中国人群miR-449a单核苷酸多态性与胃癌易感性的相关性研究[J].现代检验医学杂志,2016,31(04):14-18.[doi:10.3969/j.issn.16717-414.2016.04.004]
　ZHANG Yan-mei,MA Jing-hua,LIU Yang-chen,et al.Correlation Study on miR-449a Gene Polymorphism of Single Nucleotide and Susceptibility to Gastric Cancer in A Chinese Han Population[J].Journal of Modern Laboratory Medicine,2016,31(04):14-18.[doi:10.3969/j.issn.16717-414.2016.04.004]
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中国人群miR-449a单核苷酸多态性与胃癌易感性的相关性研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第31卷
期数:
2016年04期
页码:
14-18
栏目:
论著
出版日期:
2016-08-10

文章信息/Info

Title:
Correlation Study on miR-449a Gene Polymorphism of Single Nucleotide and Susceptibility to Gastric Cancer in A Chinese Han Population
文章编号:
1671-7414(2016)04-014-05
作者:
张艳梅1; 马靖华2; 刘阳晨3; 刘 君3; 周 娟3
1.榆林市第二医院检验科,陕西榆林 719000;
2.榆林市第一医院检验科,陕西榆林 719000;
3.泰兴市人民医院肿瘤科,江苏泰兴 225400
Author(s):
ZHANG Yan-mei1; MA Jing-hua2; LIU Yang-chen3; LIU Jun3; ZHOU Juan3
1.Department of Clinical Laboratory,the Second Hospital of Yulin City,Shaanxi Yulin 719000,China;
2.Department of Clinical Laboratory,the First Hospital of Yulin City,Shaanxi Yulin 719000, China;
3.Department of Oncology,Taixing People's Hospital,Jiangsu Taixing 225400,China
关键词:
胃癌;  miR-449a;  多态性
分类号:
R735.2; R730.43
DOI:
10.3969/j.issn.16717-414.2016.04.004
文献标志码:
A
摘要:
目的 探讨miR-449a rs112310158基因多态性与胃癌易感性的关系。方法 共纳入448例胃癌患者和452例健康对照者。miR-449a rs112310158基因型检测采用聚合酶链反应结合直接测序方法。miR-449a表达水平检测采用荧光定量PCR方法。此单核苷酸多态性位点功能由RT-PCR和免疫组化试验验证。结果 相对于对照组,胃癌病例组在吸烟者(OR=1.345,95%CI=1.028～1.761)、饮酒者(OR=1.910,95%CI=1.465～2.490)、有肿瘤家族史者(OR=4.178,95%CI=1.554～11.231)、幽门螺杆菌感染率较高者(OR=1.428,95%CI=1.098～1.857),差异均具有统计学意义。相较AA基因型,GG基因型显著增加胃癌的发病风险(OR=2.542,95%CI:1.304～4.954,P=0.005)。相较于A等位基因,携带G等位基因的个体罹患胃癌的风险升高(OR=1.279,95%CI:1.012～1.617,P=0.043)。GG型患者比AA型患者miR-449a表达水平下降。与AA基因型相比,miR-449a靶基因PRKCE在GG基因型胃癌患者中有更高的表达。结论 该研究发现miR-449a rs112310158是胃癌的遗传易感因素之一。
Abstract:
Objective To investigate the relationship of agenetic variant at miR-449a and the risk of gastric cancer.MethodsThe polymerase chain reaction(PCR)and direct sequencing were used to genotype sequence variants of miR-449a in 448 gastric cancer(GC)cases and 452 controls.The miR-449a levels were measuredby quantitative real-time PCR.The function of rs112310158 was confirmed by RT-PCR and immunohistochemistry assay.Results GC cases were more likely to be cigarette smokers(OR=1.345,95% CI=1.028～1.761)and alcohol drinkers(OR=1.910,95% CI=1.465～2.490),had cancer history in the first relatives(OR=4.178,95% CI=1.554～11.231),and have higher infection rateof Helicobacter pylori(OR=1.428,95% CI=1.098～1.857).Individuals carryingthe GG genotypes for the rs112310158 were associated significantly with increased risk of gastric cancer comparing with those carrying wild-type homozygous AAgenotypes(OR=2.542,95%CI:1.304～4.954,P=0.005).Furthermore,the Gallele increased the risk of occurrence of gastric cancer compared to the A allele(OR=1.279,95% CI:1.012～1.617,P=0.043).rs112310158 was associatedwith the expressionof miR-449a and its target gene.Conclusion A genetic variant at miR-449a may play an important role in the development of gastric cancer.

参考文献/References:

[1] Ferlay J,Shin HR,Bray F,et al.Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008[J].Int J Cancer,2010,127(12):2893-2917.
[2] Correa P.Human gastric carcinogenesis:a multistep and multifactorial process-First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention[J].Cancer Res,1992,52(24):6735-6740.
[3] Kelley JR, Duggan JM. Gastric cancer epidemiology and risk factors[J].J Clin Epidemiol,2003,56(1):1-9.
[4] Milne AN,Carneiro F,O'Morain C,et al.Nature me-ets nurture:molecular genetics of gastric cancer[J].Hum Genet,2009,126(5):615-628.
[5] Condorelli G,Latronico MV,Cavarretta E.microRN-As in cardiovascular diseases:current knowledge and the road ahead[J].J Am Coll Cardiol,2014,63(21):2177-2187.
[6] Link A, Kupcinskas J, Wex T,et al.Macro-role of microRNA in gastriccancer[J].Dig Dis,2012,30(3):255-267.
[7] Pan HW,Li SC,Tsai KW.MicroRNA dysregulation in gastric cancer[J].Curr Pharm Des,2013,19(7):1273-1284.
[8] Bartel DP.MicroRNAs:genomics,biogenesis,mechanism,and function[J].Cell,2004,116(2):281-297.
[9] Bartel DP.MicroRNAs:target recognition and regulatory functions[J].Cell,2009,136(2):215-233.
[10] Shukla GC,Singh J,Barik S.MicroRNAs:Processing,Maturation,Target Recognition and Regulatory Functions[J].Mol Cell Pharmacol,2011,3(3):83-92.
[11] Ni Q,Ji A,Yin J,et al.Effects of two common polymorphisms rs2910164in miR-146a and rs11614913 in miR-196a2 on gastric cancer susceptibility[J].Gastroenterol Res Pract,2015(2015):764163.
[12] Hua HB,Yan TT,Sun QM.miRNA polymorphisms and risk of gastric cancer in Asian population[J].World J Gastroenterol,2014,20(19):5700-5707.
[13] Chen WH,Xin PL,Pan QX,et al.ERCC1 single nucleotide polymorphism C8092A,but not its expression is associated with survival of esophageal squamous cell carcinoma patients from Fujian province,China[J].PLoS One,2014,9(9):e106600.
[14] Jeon HS,Lee SY,Lee EJ,et al.Combining microRNA-449a/b with a HDAC inhibitor has a synergistic effect on growth arrest in lung cancer[J].Lung Cancer,2012,76(2):171-176.
[15] Buurman R,Gurlevik E,Schaffer V,et al.Histone deacetylases activatehepatocyte growth factor signaling by repressing microRNA-449 in hepatocellularcarcinoma cells[J].Gastroenterology,2012,143(3):811-820,e1-15.
[16] Bou Kheir T,Futoma-Kazmierczak E,Jacobsen A,et al.miR-449 inhibitscell proliferation and is down-regulated in gastric cancer[J].Mol Cancer,2011(10):29.
[17] Noonan EJ,Place RF,Pookot D,et al.miR-449a targets HDAC-1 and induces growth arrest in prostate cancer[J].Oncogene,2009,28(14):1714-1724.
[18] Noonan EJ,Place RF,Basak S,et al.miR-449a causes Rb-dependent cellcycle arrest and senescence in prostate cancer cells[J].Oncotarget,2010,1(5):349-358.
[19] 张 旗,何湘君,马丽萍,等.p53通路微小RNA在卵巢癌细胞和浆液性卵巢癌组织中的表达及意义[J].中华肿瘤杂志,2011,33(12):885-890. Zhang Q,He XJ,Ma LP,et al.Expression and significance of microRNAs inthe p53 pathway in ovarian cancer cells and serous ovarian cancer tissues[J].Chin J Oncol,2011,33(12):885-890.
[20] Yang X,Feng M,Jiang X,et al.miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb-E2F1 activity through afeedback loop by targeting CDK6 and CDC25A[J].Genes Dev,2009,23(20):2388-2393.
[21] Chen H,Lin YW,Mao YQ,et al.MicroRNA-449a acts as a tumor suppressorin human bladder cancer through the regulation of pocket proteins[J].CancerLett,2012,320(1):40-47.
[22] Lize M,Pilarski S,Dobbelstein M.E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis[J].Cell Death Differ,2010,17(3):452-458.
[23] Li X,Li H,Zhang R,et al.MicroRNA-449a inhibits proliferation and induces apoptosis by directly repressing E2F3 in gastric cancer[J].Cell PhysiolBiochem,2015,35(5):2033-2042.
[24] Hu J,Fang Y,Cao Y,et al.MiR-449a regulates proliferation and chemosensitivity to cisplatin by targeting cyclin D1 and BCL2 in SGC7901 cells[J].Dig Dis Sci,2014,59(2):336-345.
[25] Cameron AJ,Escribano C,Saurin AT,et al.PKC maturation is promoted bynucleotide pocket occupation in dependently of intrinsic kinase activity[J].Nat Struct Mol Biol,2009,16(6):624-630.
[26] Jain K,Basu A.The multifunctional protein kinase C-epsilon in cancerdevelopment and progression[J].Cancers(Basel),2014,6(2):860-878.
[27] Basu A.The potential of protein kinase C as a target for anticancer treatment[J].Pharmacol Ther,1993,59(3):257-280.
[28] 徐 焰,赵 芳,柯 涛,等.铅暴露对大鼠体内离子浓度及相关PKC信号通路分子的影响[J].现代检验医学杂志,2012,27(5):6-9. Xu Y,Zhao F,Ke T,et al.Impact of lead exposure on the level of ion concentration and PKC signaling pathway moleculars in rats[J].Journal of ModernLaboratory Medicine,2012,27(5):6-9.
[29] Steinberg SF.Structural basis of protein kinase C isoform function[J].Physiol Rev,2008,88(4):1341-1378.
[30] Gorin MA,Pan Q.Protein kinase C epsilon:an onco-gene and emerging tumor biomarker[J].Mol Cancer,2009(8):9.

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备注/Memo

备注/Memo:

作者简介:张艳梅(1974-),女,本科,主管检验师,专业:分子生物技术。
更新日期/Last Update: 2016-08-10