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miRNA-29b-RTKN 对人乳腺癌细胞凋亡的影响及机制研究

孔 向阳, 徐 小平, 姜贻 乾*

摘要

目的 研究微小 RNA(microRNA,miRNA)-29b-Rhotekin(RTKN)对乳腺癌细胞凋亡的影响及其分子生物学机制。
方法 构建 RTKN 过表达、miRNA-29b 过表达细胞,将细胞分组为 1)NC/ 空载体组、2)RTKN 过表达组、3)miRNA-
29b 过表达组、4)miRNA-29b&RTKN 均过表达组、5)miRNA-29b 过表达 +NF-κB 抑制剂组、6)NF-κB 抑制剂组,
采用流式细胞法对各组细胞进行凋亡率及细胞周期分布情况的测定,同时利用 Western blot 法分析细胞周期相关因子(包
括 cyclinD1、c-myc、CDK1、CDK2、MCM6)和细胞抗凋亡相关因子(如 c-IAP2、BCL-xL)的表达情况。结果 与 NC/
空载体组相比,RTKN 过表达组细胞周期相关蛋白及细胞抗凋亡相关因子的表达显著提高(p<0.05),肿瘤细胞凋亡率明
显下降(p<0.01),而 miRNA-29b 过表达细胞实验结果则恰好相反(p<0.05)。与 NC 组相比,miRNA-29b 过表达组
及 NF-κB 抑制剂组的肿瘤细胞周期相关蛋白及细胞抗凋亡相关因子的表达显著减少(p<0.05),细胞 G0/G1 期显著延长
(p<0.05),肿瘤细胞的凋亡率也明显提高(p<0.01);与 miRNA-29b 过表达组及 NF-κB 抑制剂组相较,miRNA-29b
过表达 +NF-κB 抑制剂组的肿瘤细胞周期相关蛋白及细胞抗凋亡相关因子的表达显著减少(p<0.05),细胞 G0/G1 期显
著延长(p<0.05),肿瘤细胞的凋亡率也较之明显提高(p<0.01)。结论 miRNA-29b-RTKN 对乳腺癌细胞的凋亡的调控
是通过 NF-κB 信号通路实现的,可以为乳腺癌药物的研发及治疗提供新的方向。

关键词

乳腺癌;miRNA-29b;RTKN;NF-κB 通路;分子机制

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