miR-203-5p靶向调控ERBB4基因参与子宫内膜癌细胞凋亡

Chinese Journal of Human Sexuality(2019)

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Abstract
目的 探究microRNA-203-5p(miR-203-5p)靶向调控H编码人表皮生长因子受体4的癌基因(oncogene encoding human epidermal growth factor receptor 4,ERBB4)对子宫内膜癌小鼠细胞凋亡的影响和作用机制.方法 随机选取18只SPF级雄性C57/BL6小鼠,依据随机数字表法将其分为常规组和模型组,构建子宫内膜癌小鼠模型;TargetScan预测miR-203-5p靶基因;构建ERBB4的siRNA表达载体;免疫组化检测ERBB4表达情况;将传代培养后取对数期细胞用于实验,将细胞分为Blank组、Negative control (NC)组、miR-203-5p mimic组、miR-203-5p inhibitor组、si-ERBB4组、miR-203-5p mimic+si-ERBB4组;采用MTT法测定各组细胞的增殖情况;采用流式细胞术检测各组细胞凋亡情况;采用RT-PCR法和western blot法测定相关mRNA和蛋白表达量.结果 miR-203-Sp靶向ERBB4;miR-203-5p在子宫内膜癌小鼠子宫内膜组织中为低表达,ERBB4为高表达;与Blank组相比,miR-203-5p mimic+si-ERBB4组细胞凋亡率上升且增殖明显抑制,miR-203-5p inhibitor组结果相反;与Blank组相比,miR-203-5p表达在miR-203-5p mimic组和miR-203-5pmimic+si-ERBB4组中上升,在miR-203-5p inhibitor组中结果相反;与Blank组相比,在miR-203-5p inhibitor组中bcl-2表达上升而bax、Caspase-3下降,在miR-203-5p mimic组、si-ERBB4组和miR-203-5p mimic+si-ERBB4组中结果相反;与Blank组相比,ERBB4mRNA及蛋白表达在miR-203-5p mimic组、si-ERBB4组和miR-203-5p mimic+si-ERBB4组下降.结论 miR-203-5p在子宫内膜癌小鼠子宫内膜组织中低表达,ERBB4高表达.诱导miR-203-5p表达,可以通过靶向下调ERBB4基因,上调bax、Caspase-3表达并下调bcl-2表达,从而抑制其细胞侵袭,诱导其发生凋亡.
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