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CagA作用于胃癌细胞调控miR-142-3p表达作用与机制

吴蕾蕾 姜飞 陈晓伟 沈伟涛 许锐 沈孝兵

吴蕾蕾, 姜飞, 陈晓伟, 沈伟涛, 许锐, 沈孝兵. CagA作用于胃癌细胞调控miR-142-3p表达作用与机制[J]. 中国公共卫生. doi: 10.11847/zgggws1135771
引用本文: 吴蕾蕾, 姜飞, 陈晓伟, 沈伟涛, 许锐, 沈孝兵. CagA作用于胃癌细胞调控miR-142-3p表达作用与机制[J]. 中国公共卫生. doi: 10.11847/zgggws1135771
WU Lei-lei, JIANG Fei, CHEN Xiao-wei, . Effect and mechanism of CagA on miR-142-3p expression regulation in gastric cancer cells[J]. Chinese Journal of Public Health. doi: 10.11847/zgggws1135771
Citation: WU Lei-lei, JIANG Fei, CHEN Xiao-wei, . Effect and mechanism of CagA on miR-142-3p expression regulation in gastric cancer cells[J]. Chinese Journal of Public Health. doi: 10.11847/zgggws1135771

CagA作用于胃癌细胞调控miR-142-3p表达作用与机制

doi: 10.11847/zgggws1135771
详细信息
    作者简介:

    吴蕾蕾(1995 – ),女,山西吕梁人,硕士,研究方向:胃癌

    通讯作者:

    沈孝兵,E-mail:xb.shen@seu.edu.cn

  • 中图分类号: R 735.2

Effect and mechanism of CagA on miR-142-3p expression regulation in gastric cancer cells

  • 摘要:   目的   幽门螺杆菌(Helicobacter pylori,Hp)主要毒力因子细胞毒素相关蛋白A(cytotoxin-associated gene A,CagA)在胃癌的发生发展中具有重要作用。微小RNA(miRNA)可通过影响下游mRNA分子的表达进而发挥促癌或抑癌作用,本研究探讨CagA相关的miRNA及其参与胃癌进展的作用机制,以期为CagA感染胃癌患者的诊断与治疗提供新思路。  方法  在GEO数据库和TCGA数据库中筛选与Hp和胃癌均相关的miRNA,并对其进行基于TCGA数据的临床病理资料分析。构建CagA原核表达系统,以不同浓度CagA转染胃癌AGS细胞,采用实时荧光定量聚合酶链式反应(qRT-PCR)法检测目标miRNA的表达。最后借助DIANA mirPath 3.0在线网站对miRNA进行GO和KEGG分析。  结果  通过GEO、TCGA数据库及细胞实验确认miR-142-3p与感染CagA的胃癌相关。人群水平上发现mir-142 与男性胃癌Ⅰ期患者、女性45 ~ 54和55 ~ 64岁胃癌患者预后均明显相关(P < 0.05)。细胞水平上发现miR-142-3p在胃癌AGS细胞中表达上调(P < 0.01),且表达水平受CagA蛋白感染的影响(P < 0.01)。预测发现PIK3R2、PIK3R5和PIK3CD可能作为miR-142-3p下游靶标参与miR-142-3p在胃癌进展中的作用。  结论  miR-142-3p可能是CagA感染胃癌患者的潜在的治疗靶标,并可能通过PIK3R2/PIK3R5/PIK3CD发挥对胃癌进展的促进作用。
  • 图  1  TCGA数据库中mir-142mir-375表达情况及mir-142预后分析

    注:a mir-142表达量散点图;b mir-375表达量散点图;c mir-142表达量与男性Ⅰ期胃癌患者生存曲线图;d mir-142表达量与45~54年龄段女性胃癌患者生存曲线图;e mir-142表达量与55~64岁年龄段女性胃癌患者生存曲线图。

    表  1  miR-375miR-142-3p在3个数据集中表达水平信息

    数据集miRNA|LogFC|P
    GSE23739miR-142-3p2.161.30 × 10 – 4
    miR-3751.580.001
    GSE93415miR-142-3p1.502.66 × 10 – 3
    miR-3751.063.30 × 10 – 3
    GSE19769miR-142-3p1.230.008
    miR-3751.333.88 × 10 – 4
    下载: 导出CSV

    表  2  miR-142-3p在GES-1和AGS中的相对表达情况

    组别ΔCт(${\bar x} \pm {{s} }$)2-ΔΔCтt P
    GES-120.108 ± 0.4481.000– 27.757< 0.01
    AGS15.409 ± 0.08625.143
    下载: 导出CSV

    表  3  CagA粗蛋白染毒后miR-142-3p相对表达情况

    组别ΔCт(${{\bar x} } \pm {{s} }$)2-ΔΔCтt P
    1 : 50 对照组 14.567 ± 0.081 1.000 – 7.398 < 0.01
    CagA粗蛋白 11.362 ± 0.387 8.605
    1 : 100 对照组 12.545 ± 0.357 1.000 – 7.331 < 0.01
    CagA粗蛋白 11.147 ± 0.146 2.588
    1 : 200 对照组 11.501 ± 0.134 1.000 – 4.592 < 0.01
    CagA粗蛋白 10.609 ± 0.232 1.867
    下载: 导出CSV

    表  4  miR-142-3p 靶基因GO分析

    基因功能GO注释P
    细胞组分 细胞器(GO 0043226) 3.19 × 10 – 70
    细胞组分(GO 0005575) 1.22 × 10 – 15
    细胞质基质(GO 0005829) 1.02 × 10 – 14
    核浆(GO 0005654) 1.27 × 10 – 11
    蛋白质复合体(GO 0043234) 4.23 × 10 – 11
    生物学进程 细胞氮素化合物代谢过程(GO 0034641) 1.02 × 10 – 36
    生物合成过程(GO 0009058) 2.39 × 10 – 25
    基因表达(GO 0010467) 2.75 × 10 – 20
    细胞蛋白修饰过程(GO 0006464) 1.38 × 10 – 19
    寄生,寄生共生(GO 0044403) 1.29 × 10 – 13
    分子功能 离子结合(GO 0043167) 3.98 × 10 – 24
    分子功能(GO 0003674) 1.08 × 10 – 17
    酶结合(GO 0019899) 3.03 × 10 – 10
    核酸结合转录因子活性(GO 0001071) 7.79 × 10 – 9
    RNA 结合(GO 0003723) 2.16 × 10 – 6
    下载: 导出CSV

    表  5  miR-142-3p 靶基因KEGG通路分析

    KEGG 通路P Genes
    赖氨酸退化(hsa00310) 6.22 × 10 – 4 WHSC1L1、ASH1L、KMT2D、DOT1L、WHSC1、KMT2A、ALDH9A1、PLOD1
    雌激素信号通路(hsa04915) 1.40 × 10 – 3 ATF2、GNAS、CREB5、PIK3R2、PIK3R5、PRKCD、AKT2、PIK3CD、KCNJ6、GNAQ、
    CREB3L2、HSPA1B、ITPR3、ITPR2
    黏着小带(hsa04520) 9.72 × 10 – 3 TGFBR1、WASL、CTNND1、PTPRF、SMAD4、CTNNB1、PTPRJ、RAC1、SSX2IP、YES1
    细菌侵袭上皮细胞(hsa05100) 0.010 WASL、CRK、PIK3R2、PIK3R5、ARPC1B、CTTN、HCLS1、PIK3CD、CTNNB1、CLTA、RAC1、GAB1
    病毒致癌作用(hsa05203) 0.010 ATF2、GTF2H1、CREB5、PIK3R2、PIK3R5、CDKN1B、HIST1H2BD、EIF2AK2、SND1、PIK3CD、SKP2、EGR2、JAK3、RAC1、KAT2B、CASP8、CREB3L2、HIST2H2BE、LYN、
    MDM2、UBR4、HIST1H4D
    胰腺癌(hsa05212) 0.010 TGFBR1、E2F2、PIK3R2、PIK3R5、AKT2、PIK3CD、SMAD4、RAC1、BCL2L1
    癌症中的蛋白聚糖(hsa05205) 0.045 FZD7、PIK3R2、PIK3R5、ROCK2、MAPK13、CTTN、VAV2、AKT2、ITGAV、ANK3、HCLS1、PIK3CD、CTNNB1、PTPN11、RAC1、GAB1、ITPR3、ITPR2、MDM2
    致病性大肠杆菌感染(hsa05130) 0.047 WASL、ROCK2、ARPC1B、CTTN、HCLS1、ARHGEF2、TLR5、CTNNB1、NCK2、TUBAL3
    下载: 导出CSV
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  • 收稿日期:  2021-06-07
  • 网络出版日期:  2022-03-23

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