Effect of targeted regulation of ABCG2 signaling pathway by miR-144-3p on invasion and migration of gastric cancer cells
- Author:
- No author available
- Journal Title:
- World Chinese Journal of Digestology
- Issue:
- 28
- DOI:
- 10.11569/wcjd.v26.i28.1635
- Key Word:
- miR-144-3p;ATP结合转运蛋白G家族成员2;胃癌细胞;基质金属蛋白酶;侵袭和迁移
Abstract： 目的 研究miR-144-3p靶向调控ATP结合转运蛋白G家族成员2(ATP-binding transporter Gfamily member 2,ABCG2)对胃癌(gastric cancer,GC)HGC-27细胞侵袭和迁移能力的影响,并对其作用机制进行初步探讨.方法 通过qRT-PCR检测人GCHGC-27细胞株和人胃黏膜上皮GES-1细胞株中miR-144-3p和ABCG2的表达情况;通过靶基因预测软件预测miR-144-3p和ABCG2靶向结合位点,通过双荧光素酶报告基因实验检测二者靶向结合关系;通过qRT-PCR检测miR-144-3pmimic或miR-144-3p inhibitor转染GC细胞后miR-144-3p及ABCG2的表达水平;通过明胶酶谱实验检测对转染ABCG2 siRNA的GC细胞中基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)活性的影响;通过Transwell侵袭和迁移实验检测转染miR-144-3p mimic、miR-144-3p inhibitor、ABCG2siRNA对GC细胞侵袭和迁移能力的影响,结果 与正常细胞组人胃黏膜上皮GES-1细胞株相比,GC细胞组人GCHGC-27细胞株中miR-144-3p的表达量明显降低,ABCG2的表达水平明显升高,差异具有统计学意义(P＜0.05);靶基因预测miR-144-3p和ABCG23'UTR存在结合位点,双荧光素酶报告基因实验证实了miR-144-3p和ABCG2靶向结合关系;与对照组相比,转染miR-144-3p mimic组GC细胞中miR-144-3p的表达明显升高,ABCG2的表达明显降低,细胞侵袭和迁移能力显著降低,差异具有统计学意义(P＜0.05),转染miR-144-3p inhibitor则表现出相反的作用;明胶酶谱实验检测结果表明ABCG2 siRNA转染可显著抑制GC细胞中MMP-2和MMP-9蛋白活性,抑制GC细胞侵袭和迁移能力,差异具有统计学意义(P＜0.05).结论 MiR-144-3p能够抑制GC细胞侵袭和迁移能力,其作用机制与靶向调控ABCG2-MMP-2/9信号通路有关,
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