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非編碼RNAs miR-141/miR-22和PVT1調(diào)控胃癌生長和轉(zhuǎn)移的作用與機制研究

發(fā)布時間:2021-06-22 02:59
  研究背景與意義:胃癌(gastric cancer)是世界范圍內(nèi)第五大流行的惡性腫瘤,同時其引起的相關(guān)死亡在癌癥領(lǐng)域內(nèi)位列第三。據(jù)2015年發(fā)表的《Global cancer statistics,2012》的最新統(tǒng)計數(shù)據(jù)顯示:在2012年全球范圍內(nèi)預估胃癌新發(fā)患者有951600例,胃癌患者死亡病例為723100例。盡管在胃癌的診斷治療領(lǐng)域取得了不斷的進展,但我國胃癌患者的5年生存率仍舊較低,且惡性胃癌的中位生存期仍然沒有顯著的提高。因此,深入研究胃癌發(fā)生進程中的分子機制,為胃癌患者提供新的診斷治療方式和策略具有重要的意義。芯片和高通量測序技術(shù)對基因組和轉(zhuǎn)錄組學的研究表明僅少于2%的基因組用來編碼蛋白,而大于75%的基因組被激活轉(zhuǎn)錄為非編碼RNAs。新近研究表明,腫瘤基因組中的多個突變位點位于非編碼蛋白的區(qū)域,而這些區(qū)域通常會轉(zhuǎn)錄為微小RNAs(mi RNAs)和長鏈非編碼RNAs(long non-coding RNAs,lncRNAs)。二代測序結(jié)果表明,多個miRNAs和lncRNAs的表達異常與多種腫瘤的發(fā)生與進程相關(guān),這些異常表達的mi RNAs和lncRNAs在基因表達調(diào)控... 

【文章來源】:中國人民解放軍陸軍軍醫(yī)大學重慶市

【文章頁數(shù)】:147 頁

【學位級別】:博士

【部分圖文】:

非編碼RNAs miR-141/miR-22和PVT1調(diào)控胃癌生長和轉(zhuǎn)移的作用與機制研究


miR-141在胃癌組織中表達下調(diào),其表達與胃癌的轉(zhuǎn)移能力成負相關(guān)Figure1.MiR-141isdownregulatedinprimarytumortissuesofGCandcorrelatesinverselywithmetastaticcapacityinGCtissue.(A)Differentialexpressionof16miRNAsbetweenpairedGCandnormalmucosa(NM)

胃癌細胞系,過表達


37圖 2. miR-141 的過表達抑制胃癌細胞系的增殖,侵襲和遷移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

胃癌細胞系


39圖 3. 抑制 miR-141 的表達,促進胃癌細胞系 AGS 細胞的增殖,遷移和侵襲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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