Y盒结合蛋白1调控上皮细胞间质转化促进结直肠癌发生发展-外科学(普通外科学)专业论文.docxVIP

Y 盒结合蛋白 Y 盒结合蛋白 1 调控上皮细胞间质转化促进结直肠癌发生发展 中文摘要 II II 抑制（P0.05），并且上皮标记物 E 钙黏蛋白的表达上调、间质标记 物 N 钙黏蛋白和波形蛋白表达下调；结直肠癌组织中 YB-1 的表达水 平与 E 钙黏蛋白的表达水平呈负相关，而与 N 钙黏蛋白和波形蛋白的 表达水平呈正相关（P0.05）。3. 结直肠癌组织中 N 钙黏蛋白表达水 平明显高于其在癌旁正常组织中表达水平，并且与 E 钙黏蛋白的表达 水平呈负相关。N 钙黏蛋白表达水平与肿瘤分化程度、肿瘤大小、肿 瘤侵犯、淋巴结转移有显著相关性（P0.05）。此外，N 钙黏蛋白表 达水平也是是影响结直肠癌患者总体生存率的独立因素。下调 N 钙黏 蛋白表达水平后，结肠腺癌细胞 HT-29 的增殖和迁移能力受到抑制 （P0.05），并且 E 钙黏蛋白的表达上调。 结论：YB-1 通过调控 EMT 促进结直肠癌的发生发展。EMT 过程中 间质标记物 N 钙黏蛋白在结直肠癌发展过程中也发挥着重要作用。通 过靶向 YB-1 抑制 EMT 有望成为治疗结直肠癌的新策略。 关键词：Y 盒结合蛋白 1；结直肠癌；上皮细胞间质转化；N 钙 黏蛋白 作者：严雪冰 指导教师：金志明 PAGE PAGE IV Y-box binding protein?1 promotes the initiation and progression of colorectal cancer by regulating Epithelial Mesenchymal Transition Abstract Objective：To explore the biological role and related molecular mechanism of Y?box binding protein?1(YB-1) in the initiation and progression of colorectal cancer (CRC). Methods: 1.Immunohistochemistry was performed to detect expression of YB-1 in 170 primary CRC tissues and their matched normal tissues, and its clinical significance was evaluated by statistical methods. 2. Small interfering RNA (siRNA) was performed to downregulate YB-1 expression in HT-29 colon adenocarcinoma cells. MTT assay, apoptosis assay, transwell migration and invasion assay were then employed to investigate the biological role of cancer cells. RT-PCR and western blot were employed to detect the expression of Epithelial Mesenchymal Transition (EMT) markers in cancer cells. The expression of YB-1 and EMT markers in 80 CRC tissues were detected by Immunohistochemistry. The relationship between YB-1 and EMT markers was identified by correlation analysis. 3. The expression of N-cadherin in CRC tissues and their matched nomal tissues was detected by western blot and Immunohistochemistry. The siRNA was then employed to downregulate the expression of N-cadherin in HT-29 colon adenocarcinoma cells. The proliferative and migratory ability of cancer cells were subsequently evaluated by MTT