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非编码RNAs miR-141/miR-22和PVT1调控胃癌生长和转移的作用与机制研究

发布时间:2021-06-22 02:59
  研究背景与意义:胃癌(gastric cancer)是世界范围内第五大流行的恶性肿瘤,同时其引起的相关死亡在癌症领域内位列第三。据2015年发表的《Global cancer statistics,2012》的最新统计数据显示:在2012年全球范围内预估胃癌新发患者有951600例,胃癌患者死亡病例为723100例。尽管在胃癌的诊断治疗领域取得了不断的进展,但我国胃癌患者的5年生存率仍旧较低,且恶性胃癌的中位生存期仍然没有显著的提高。因此,深入研究胃癌发生进程中的分子机制,为胃癌患者提供新的诊断治疗方式和策略具有重要的意义。芯片和高通量测序技术对基因组和转录组学的研究表明仅少于2%的基因组用来编码蛋白,而大于75%的基因组被激活转录为非编码RNAs。新近研究表明,肿瘤基因组中的多个突变位点位于非编码蛋白的区域,而这些区域通常会转录为微小RNAs(mi RNAs)和长链非编码RNAs(long non-coding RNAs,lncRNAs)。二代测序结果表明,多个miRNAs和lncRNAs的表达异常与多种肿瘤的发生与进程相关,这些异常表达的mi RNAs和lncRNAs在基因表达调控... 

【文章来源】:中国人民解放军陆军军医大学重庆市

【文章页数】:147 页

【学位级别】:博士

【部分图文】:

非编码RNAs miR-141/miR-22和PVT1调控胃癌生长和转移的作用与机制研究


miR-141在胃癌组织中表达下调,其表达与胃癌的转移能力成负相关Figure1.MiR-141isdownregulatedinprimarytumortissuesofGCandcorrelatesinverselywithmetastaticcapacityinGCtissue.(A)Differentialexpressionof16miRNAsbetweenpairedGCandnormalmucosa(NM)

胃癌细胞系,过表达


37图 2. miR-141 的过表达抑制胃癌细胞系的增殖,侵袭和迁移Figure 2. The effect of ectopic expression of miR-141 levels on cell proliferation, migration andinvasion of HGC-27 in vitro.(A) MiR-141 effectively increased miR-141 expression level, as determined using real time PCRin HGC-27 cell line, which was normalized against U6 RNA. Data are presented as mean±S.D. (n= 3).(B)Overexpression of miR-141 by miR-141 mimics affected the cell proliferation of HGC-27 cells asdetermined using CCK8 assay. Data are presented as mean±S.D. (n= 6). (C, D) Overexpression ofmiR-141 by miR-141 mimics affects the migration capacity of HGC-27 cells as determined using theWound healing assay. Representative images were captured at 0 h and 48 h after transfection. Therelative wound breadth remain (100%) represents the migration capacity of gastric cancer cells, andthe breadth at 0 h was set as 100%. All of the experiments were performed three times. Data are

胃癌细胞系


39图 3. 抑制 miR-141 的表达,促进胃癌细胞系 AGS 细胞的增殖,迁移和侵袭Figure 3. The effect of inhibition of miR-141 levels on cell proliferation,migration and invasion of AGS in vitro.(A)MiR-141 inhibitors effectively decreased miR-141 expression level, as determined using realtime PCR in AGS cell line, which was normalized against U6 RNA. Data are presented as mean±S.D.(n= 3). (B) Inhibition of miR-141 by miR-141inhibitors affected the cell proliferation of AGS cellsas determined using CCK8 assay. Data are presented as mean±S.D. (n= 6). (C, D) Inhibition ofmiR-141 by miR-141 inhibitors affects the migration capacity of AGS cells as determined using theWound healing assay. Representative images were captured at 0 h and 48 h after transfection. Therelative wound breadth remain (100%) represents the migration capacity of gastric cancer cells, andthe breadth at 0 h was set as 100%. All of the experiments were performed three times. Data are


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