中国广西人群miR-146a、miR-149 基因遗传多态性的研究

目的：研究广西人群miR-146a C>G (rs2910164）、miR-149 T>C（rs2292832）等位基因及基因型频率分布,分析其与不同民族种族间的差异性。方法：采用单碱基延伸技术和DNA测序技术对303例广西人群中miR-146a C>G和miR-149 T>C基因单核苷酸多态性(SNP)位点进行分型检测,并与人类基因组计划 (Hapmap) 数据库中公布的非洲人、欧洲人、日本人和中国北京人群的SNP分型数据比较。结果：miR-146a C>G、miR-149 T>C等位基因和基因型频率在广西男女人群之间分布均无差异性（P均>0.05）。广西人群miR-146a C>G和miR-149 T>C基因型及等位基因频率与非洲人、欧洲人、中国北京人比较有统计学意义（P均<0.05）。结论：广西人群miR-146a C>G和miR-149 T>C存在基因多态性,与其他种族人群比较有差异性,这种差异性对人类遗传病的研究可能会起到重要作用。     

MicroRNA-17-92基因对胃癌干细胞更新和增殖的影响

背景：研究表明,miRNA对肿瘤干细胞的更新分化有调节作用,有关miRNA-17-92在胃癌干细胞更新及增殖中的作用尚未完全阐明。 目的：分析miRNA-17-92在胃癌干细胞自我更新及增殖中的作用。 方法：①利用细胞培养使胃癌干细胞贴壁分化并送miRNA芯片检测,寻找并验证不断缺失的miRNA。②构建并转染miRNA-17-92分子慢病毒稳定转染细胞。③通过tumorsphere实验研究miRNA-17-92与胃癌细胞更新的关系。④通过MTT、平板克隆试验检测miRNA-17-92与胃癌干细胞增殖的关系。 结果与结论：①miR-19b/20a/92a在胃癌干细胞贴壁分化过程中表达逐渐减低。②慢病毒携带的miRNA-17-19基因在MKN28细胞和CD44-/EpCAM-细胞中的表达均明显增加;瞬时转染pre-miR-19b/20a/92a能使CD44-/EpCAM-和MKN28的miRNA表达增高,瞬时转染pre-miR-19b/20a/92a拮抗剂能使SGC7901和CD44+/EpCAM+的miRNA表达降低;过表达lenti-miR-19b/20a/92a能显著增加胃癌细胞形成肿瘤球的能力;在化疗药的作用下,lenti-miR-19b/20a/92a感染细胞的生存时间延长;瞬时转染pre-miR-19b/20a/92a 能够显著增加CD44+/EpCAM+细胞数,转染其拮抗剂可以降低CD44+/EpCAM+细胞数。③miR-19b/20a/92a稳定表达组的胃癌细胞增殖速度较对照组快。瞬间转染miR-19b/20a/92a前体组加快胃癌细胞的增殖速度,而瞬时转染其拮抗物组减慢胃癌细胞的增殖速度;瞬间转染 miR-19b/20a/92a前体组的克隆数较对照组多,而瞬时转染miR-19b/20a/92a拮抗物组的克隆数较对照组少。结果表明miR-19b/20a/92a基因在胃癌干细胞分化过程中不断缺失,miR-17-92基因能够促进胃癌干细胞的更新和增殖。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

miR-143/145启动子区rs17723799多态性与宫颈癌易感性的相关性研究

目的:探讨miR-143/145启动子区rs17723799多态性与宫颈癌的关系.方法:选取242例宫颈癌患者及249例健康志愿者作为对照,采用SnaPshot和Sanger测序法对rs17723799进行多态性检测,对临床数据进行分层分析,qRT-PCR检测宫颈癌组织中miR-143/145相对表达.结果:rs172...     

miR-18a、miR-17和miR-20在结直肠癌组织中表达增高

目的 MicroRNAs(miRNAs)是一类在转录后调控基因表达的非编码RNA,越来越多的证据显示:一些在肿瘤中异常表达的miRNAs,有做为肿瘤诊断分子标记和判断预后的潜在价值.该研究应用miRNAs芯片技术筛选结直肠癌组织中差异表达的miRNAs,探索与结直肠癌相关的miRNAs.方法 从3对手术切除的结直肠癌和相配对的正常结直肠组织中提取总RNA,miRNA芯片检测miRNA表达情况,然后在90例配对的结直肠癌和正常结直肠组织中,用Real-time RT-PCR(Taqman)对部分差异表达miRNA进行验证.结果 与配对的正常结直肠组织相比,有22个miRNAs在结直肠癌中异常表达,其中miR-18a、miR-17和miR-20经Real-time RT-PCR(Taqman)验证,在结直肠癌组织中表达显著增高(P=0.006,0.023,0.034).结论 miR-18a、miR-17和miR-20可能参与了结直肠癌的发生过程.     

17β-雌二醇通过microRNA-29b调节NK细胞干扰素γ的分泌

目的:研究17β-雌二醇(E2)对人自然杀伤细胞株NK92中干扰素γ(IFN-γ)分泌的影响及其可能的机制。方法:用E2和poly I:C处理NK92细胞,分别在4、8、12和24小时后用实时定量PCR、酶联免疫吸附法和流式细胞术测定NK92细胞中IFN-γ的表达情况,用实时定量PCR检测microRNA-29b(miR-29b)的变化。进一步,构建含有IFN-γ3’UTR的pEGFP-C1质粒,并转染pre-29b和pEGFP-IFN-γ3’UTR质粒至HEK293A细胞中,用流式细胞术检测绿色荧光蛋白(GFP)的变化。结果:E2抑制NK92细胞的IFN-γ分泌和上调miR-29b的表达;miR-29b能够直接靶向调节IFN-γ3’UTR mRNA。结论:E2可能通过调节NK92的miR-29b而影响IFN-γ的分泌水平,进而影响其免疫功能。     

miR-17-5p通过靶向调控PTEN表达抑制乳腺癌的增殖、侵袭及迁移

目的 探讨miR-17-5p在乳腺癌中的表达和对乳腺癌细胞的调控作用及其作用机制。方法 采用RT-qPCR和Western blot方法检测乳腺癌组织和细胞中miR-17-5p和PTEN的表达;CCK-8法检测细胞增殖;流式细胞术检测凋亡,Transwell实验和划痕实验检测细胞侵袭和转移。Western blot检测PTEN蛋白表达变化;采用荧光素酶活性检测miR-17-5p与PTEN的相互作用。结果 与对照组相比,乳腺癌组织和细胞中miR-17-5p表达升高,同时PTEN水平降低。体外实验发现,miR-17-5p的敲减能够抑制乳腺癌细胞增殖和转移。荧光素酶报告基因实验发现PTEN是miR-17-5p的靶点。miR-17-5p下调促进乳腺癌细胞PTEN蛋白的表达。结论 miR-17-5p与乳腺癌患者预后相关,同时miR-17-5p下调能显著抑制乳腺癌细胞的增殖和侵袭转移。     

IL-18启动子区基因多态性与江西汉族人群哮喘的关系

目的:探讨IL-18基因启动子区-607C/A、-137G/C多态性与江西汉族人群支气管哮喘(简称哮喘)及其临床表型的关系.方法:采用序列特异性引物聚合酶链反应(PCR-SSP)和DNA测序技术对102例哮喘患者(A组)[其中合并过敏性鼻炎40例(A1组),不合并过敏性鼻炎62例(A2组)]及100例健康对照者(B组)IL-18基因启动子区1-607C/A、-137G/C基因型多态性进行检测.结果:-607C等位基因频率在A、A1、A2、B组中分别为50.0%、40.0%、56.5%、45.5%,A2和A1两组比较差异有显著性(P＜0.05);-137C等位基因频率在A、A1、A2、B组中分别为17.2%、27.5%、10.5%、16.0%,A1和B两组比较差异有显著性(P＜0.05),A1和A2比较差异有显著性(P＜0.01).-607C/-137G单倍体基因频率在A、A1、A2、B组中分别为45.1%、33.7%、52.4%、41.5%,A2和A1两组比较差异有显著性(P＜0.01);-607A/-137C单倍体基因频率在A、A1、A2、B组中分别为12.3%、21.3%、6.5%、12.0%,A1和A2两组比较差异有显著性(P＜0.01).结论:IL-18-137C等位基因与江西汉族人群哮喘合并过敏性鼻炎有关,IL-18-607C/A、-137G/C基因多态性在哮喘合并过敏性鼻炎和哮喘不合并过敏性鼻炎患者中频率分布不同.提示IL-18可能在哮喘和过敏性鼻炎发病机制中所起的作用不同.     

广西人群miRNA-107基因多态性分布特征及其与血脂的关系

目的探讨miR-107基因单核苷酸多态性(SNP)位点rs2296616 C/T在广西地区健康人群中的分布特点,对比其在不同种族间基因型及等位基因频率分布的差异,并进一步探讨rs2296616 C/T位点单核苷酸多态性(SNP)与血脂水平的相关性。方法采用多重单碱基延伸SNP分型技术(multiplex SNa Pshot)和DNA测序法,检测372例广西健康人rs2296616 C/T位点的多态性,用7600生化仪检测其血脂相关指标,并用统计学方法分别比较rs2296616C/T位点多态性在各种族人群间的分布差异及不同基因型间的血脂水平差异。结果广西人群miR-107基因rs2296616 C/T位点存在TT(91.1%)和CT(8.9%)两种基因型及T(95.6%)和C(4.4%)两种等位基因。该位点的基因型和等位基因型频率在广西人群不同性别间的比较,差异无统计学意义(P>0.05)。其基因型和等位基因频率与人类基因组单体型图(Hap Map)所公布的欧洲人、日本人、非洲人、印第安人和墨西哥人分型数据相比较,差异均有统计学意义(P<0.05),但与北京汉族人群比较,差异无统计学意义(P>0.05)。rs2296616 C/T位点两种基因型人群血脂之间比较,携带TT基因型人群的高密度脂蛋白胆固醇(HDL-C)与CT组比较,差异具有统计学意义(P<0.05)。结论广西人群miR-107基因rs2296616 C/T位点多态性与其他种族人群之间比较存在不同程度的差异;rs2296616 C/T位点多态性与HDL-C水平高低有关。     

广西瑶族与汉族人群TGF-β1基因启动子-509 C/T多态性的研究

目的研究TGF-β1(转化生长因子-β1)基因多态性在广西瑶族与汉族人群中的分布.方法应用聚合酶链反应-限制性片段长度多态性技术检测150名瑶族人和190名汉族人的TGF-β1基因多态性,比较两组人群TGF-β1基因型和等位基因的分布频率.结果在瑶族人中CC基因型占46.0%、CT基因型占43.3%、TT基因型占10.7%;在汉族人中CC基因型占30.0%、CT基因型占51.1%、TT基因型占19.9%.两组人群TGF-β1基因型的分布频率差异有显著性(P＜0.05).结论瑶族与汉族人群TGF-β1基因多态性分布频率差异有显著性.     

Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes

The genomic region encoding the miR-17-92 microRNA (miRNA) cluster is often amplified in lymphoma and other cancers, and cancer cells carrying this amplification have higher expression of miRNA in this cluster. Retroviral expression of miR-17-92 accelerates c-Myc-induced lymphoma development, but precisely how higher expression of miR-17-92 promotes lymphomagenesis remains unclear. Here we generated mice with higher expression of miR-17-92 in lymphocytes. These mice developed lymphoproliferative disease and autoimmunity and died prematurely. Lymphocytes from these mice showed more proliferation and less activation-induced cell death. The miR-17-92 miRNA suppressed expression of the tumor suppressor PTEN and the proapoptotic protein Bim. This mechanism probably contributed to the lymphoproliferative disease and autoimmunity of miR-17-92-transgenic mice and contributes to lymphoma development in patients with amplifications of the miR-17-92 coding region.     

Tumorigenicity of the miR-17-92 cluster distilled

The miR-17-92 gene cluster, with its six different mature microRNAs (miRNAs), has an established oncogenic function. However, the oncogenic contribution of each individual miRNA in the cluster has not been assigned. Two studies published in the December 15, 2009, issue of Genes & Development by Mu and colleagues (pp. 2806–2811) and Olive and colleagues (pp. 2839–2849) dissected the miR-17-92 cluster to its individual miRNA components and identified their relative contributions to oncogenic transformation in mouse model systems.     

广西人群IL-22基因多态性分布特征及其与血脂的关系

目的:研究广西正常人群中白细胞介素22(IL-22)基因rs2227485C/T和rs2227491A/G位点的多态性分布特点和在不同人群间的分布差异,探讨不同基因型间常见血脂指标水平的差异。方法:采取多重单碱基延伸法(SNa Pshot)和DNA测序相结合的方法对280例广西人群IL-22基因的rs2227485C/T和rs2227491A/G位点进行基因分型检测,并用统计学方法比较各组间多态性分布的差异及不同基因型间血脂指标水平的差异。结果:rs2227485C/T存在CC、CT和TT 3种基因型,分布频率分别为17.1%、49.3%和33.6%,此位点基因型及等位基因频率在广西人群不同性别间的差异无统计学显著性(P0.05),其基因型及等位基因与国际人类基因组单体型图计划公布的意大利、北京、日本和墨西哥人群相比,差异有统计学意义(P0.05);rs2227491A/G存在AA、AG和GG 3种基因型,分布频率分别为16.1%、52.8%和31.1%,此位点基因型及等位基因频率在广西人群不同性别间的差异无统计学显著性(P0.05),基因型频率与意大利、日本和墨西哥人群之间的差异有统计学意义(P0.05),等位基因分布频率与其他4个人群相比差异均有统计学意义(P0.05)。rs2227491A/G位点3种基因型间的HDL-C和LDL-C差异有统计学意义(P0.05),其中HDL-C在AG/AA与GG组比较差异有统计学意义(P0.05),LDL-C在AG/GG和AA组比较差异有统计学意义(P0.05)。结论:IL-22基因rs2227485C/T和rs2227491A/G位点多态性在不同人群间存在着差异。rs2227491A/G多态性与血脂水平相关。     

Interleukin 10 promoter region polymorphisms in inflammatory bowel disease in Tunisian population

Objective:  To test whether IL-10 promoter region polymorphisms are associated with susceptibility to inflammatory bowel disease, we examined the contribution of interleukin- 10 (IL-10) gene polymorphisms to Crohn’s disease (CD) and Ulcerative colitis disease (UC) occurrence and also to CD phenotype. Materiels and Methods:  SNPs at positions -627 (C > A) and −1117 (G > A) in the IL-10 promoter were determined in a sample of 105 Tunisian patients with IBD (75 CD and 30 UC) and 90 matched healthy controls. Results:  The 627 CA genotype is associated with ileal location (p = 0.015) and with stricturing (p = 510-3) and penetrating (p = 310-3) presentation of CD. An additive effect between IL10 variants and CARD15 3020 insC mutation (p = 0,006) on severe forms of CD was shown. Conclusions:  In Tunisian population, the 3020insC insertion in NOD2/CARD15 gene is a marker of susceptibility to CD, while the A allele at position -627 in the IL-10 promoter increases the risk of CD ileal location and severe disease presentation. A genetic epistasis between IL-10 gene polymorphisms and CARD15/NOD2 gene mutation was suggested. A. Moussa, S. Ouerhani, K. Bougatef : The authors have collaborated on the same level Received 29 September 2008; returned for revision 6 November 2008; received from final revision 9 November 2008; accepted by A. Falus 11 November 2008     

The polymorphisms of interleukin 17A (IL17A) gene and its association with pediatric asthma in Taiwanese population

Background:  The interleukin 17A ( IL17A ) gene, located on chromosome 6p and linked to asthma phenotype, is a highly potential candidate gene conferring asthma susceptibility. The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of IL17A and asthma in Taiwanese children.
Methods:  We selected and performed genotyping on nine SNPs that encompass the genomic region of IL17A in Taiwanese children with or without asthma. A total of 1939 subjects containing 1027 subjects in testing group and 931 subjects in validation group were recruited in this study.
Results:  After Bonferroni correction, SNP rs8193036 was found to have a weak association ( P  = 0.0074 × 9 = 0.066) in genotype frequency test. This association was confirmed by validation group. Logistic regression adjusted allergy comorbidity and gender showed a slightly weaker association.
Conclusions:  The results indicated an independent role of IL17A promoter polymorphism rs8193036 in the association with pediatric asthma in Taiwanese population.     

No association between polymorphisms in the neprilysin promoter region and Swedish Alzheimer's disease patients

Amyloid beta-peptide (Abeta) deposition in brain is important in the development of Alzheimer's disease (AD). Neprilysin (NEP) appears to be the major Abeta degrading enzyme in vivo and reduced mRNA levels of NEP correlates with increased plaque density. We hypothesized that alterations in the NEP promoter region may alter NEP expression and thus be involved in the AD process. We investigated three putative important regions in the NEP promoter region; two dinucleotide-repeats (CA and GT) and a 480 base pair fragment. With fragment analysis and sequencing, 164 early-onset and 152 late-onset Swedish AD cases and 109 non-demented controls were investigated. No significant difference in the distribution of promoter polymorphisms between AD cases and controls were found in this study.