目的 拟研究蛋白酶活化受体2(protease-activated receptor 2,PAR2)信号通路是否参与结肠肿瘤的进展.方法 利用氧化偶氮甲烷(azoxymethane,AOM)和葡聚糖硫酸钠(dextran sodium sulfate,DSS)成功建立小鼠结肠炎相关结肠癌模型,取小鼠不同阶段的结肠组织提取总RNA,逆转录为cDNA后采用实时荧光定量聚合酶链反应检测PAR2、miR-125b及Grb2协同结合蛋白2(Grb2 associated binding protein 2,Gab2)的表达水平.结果 AOM联合3个周期的DSS后,小鼠结肠可见多发的腺瘤和不典型增生;而AOM联合4个周期的DSS后,小鼠结肠腺瘤突破基底层侵入黏膜下层形成腺癌.在肿瘤进展过程中,PAR2 mRNA的表达水平显著升高,而miR-125b的表达水平则明显降低.Gab2 mRNA在腺癌中的表达水平显著高于其在腺瘤中的表达水平(P=0.0267).结论 PAR2信号通路与结肠肿瘤的局部浸润密切相关.PAR2可能通过miR-125b及其靶基因Gab2促进结肠腺瘤的局部侵袭和浸润.%ObjectiveTo explore the role of protease-activated receptor 2 (PAR2) and miR-125b in colitis- associated colorectal carcinogenesis.Method We established colitis-associated colorectal cancer model using azoxymethane (AOM) and dextran sulfate sodium (DSS). Colonic tissue were collected at different time during colitis-associated carcinogenesis. The mRNA expression of PAR2, miR-125b and Grb2 associated binding protein 2 (Gab2) were detected by real-timefluorescence quantitative PCR after reverse transcription. Result Neoplasia broke through the base membrane and invaded into the submucosa layer after 4 cycles of DSS, while it limited in mucosa layer after 3 cycles of DSS. Compared with adenoma, PAR2 expression was significantly higher and miR-125b expression was inhibited in adenocarcinoma. Moreover, the expression of miR-125b target gene Gab2 was significantly up-regulated in adenocarcinoma than adenoma.Conclusion The PAR2 signaling closely associates with the development of colitis-associated carcinogenesis in vivo. PAR2 might promote the invasion of cancer through miR-125b andGab2.
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