miR-125b通过Wnt/β-catenin信号通路促进胃癌细胞上皮间质转化和转移

被引:0
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作者
常帅
赵耀
李顺乐
张迪
张立
翟宏军
吉鸿
机构
[1] 西安交通大学第二附属医院普通外科
关键词
胃癌; 上皮间质转化(EMT); 转移; miR-125b; Wnt/β-catenin;
D O I
暂无
中图分类号
R735.2 [胃肿瘤];
学科分类号
摘要
目的 探讨miR-125b促进胃癌细胞侵袭、转移以及上皮间质转化(EMT)的分子机制。方法 应用qRT-PCR检测miR-125b在胃癌组织及其相应的癌旁组织中的表达;胃癌细胞在上调或下调miR-125b时,Western blotting检测DKK3和SERPINA4的蛋白表达,双荧光素酶报告实验验证miR-125b能否与DKK3、SERPINA4靶向结合,MKN45细胞共转染miR-125b抑制物和靶基因siRNA,用迁移、侵袭实验观察miR-125b能否通过DKK3、SERPINA4调节MKN45细胞的生物学功能,并观察EMT相关转录因子表达;进一步通过慢病毒转染胃癌细胞上调或下调血清反应因子(SRF)表达并经尾静脉注射裸鼠后观察体内实验中肺转移瘤的数目,探讨SRF对胃癌细胞转移的影响。结果 qRT-PCR结果显示miR-125b在胃癌组织的表达上调,且与临床分期和淋巴结转移相关。双荧光素酶报告实验显示DKK3和SERPINA4是miR-125b在胃癌细胞中的直接靶点,并激活Wnt/β-catenin信号通路,进而促进EMT相关转录因子Twist1和Slug的转录,诱导EMT的发生,促进胃癌转移。体内体外实验证实转录因子SRF通过正向调节miR-125b的表达促进胃癌细胞的侵袭转移。结论 SRF/miR-125b轴促进了胃癌细胞的EMT和转移,这些调节因子有望成为胃癌新的潜在治疗靶点或生物标志物。
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页码:718 / 725
页数:8
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