基础医学与临床 ›› 2017, Vol. 37 ›› Issue (6): 792-796.

• 研究论文 • 上一篇    下一篇

miR-449b介导5-氟尿嘧啶/顺铂抑制肝癌细胞的迁移

侯彭姣,邓艳春,梁娜,刘长征   

  1. 中国医学科学院基础医学研究所
  • 收稿日期:2017-03-24 修回日期:2017-04-19 出版日期:2017-06-05 发布日期:2017-05-26
  • 通讯作者: 刘长征 E-mail:cz-liu@ibms.pumc.edu.cn
  • 基金资助:
    国家自然科学基金面上项目

Inhibitory effect of 5-FU and cisplatin mediated by miR-449b on the migration of HCC cells

  • Received:2017-03-24 Revised:2017-04-19 Online:2017-06-05 Published:2017-05-26
  • Contact: Chang-Zheng LIU E-mail:cz-liu@ibms.pumc.edu.cn

摘要: 目的 研究化疗药5-氟尿嘧啶和顺铂对microRNA-449b(miR-449b)在肝癌细胞中表达的影响及其抑制肝癌细胞迁移能力的分子机制。方法 收集肝癌病人的组织样本,提取总RNA,用real-time PCR法检测肝癌组织样本中miR-449b的表达;5-氟尿嘧啶和顺铂处理肝癌细胞,检测miR-449b的表达;在肝癌细胞中过表达miR-449b或用5-氟尿嘧啶和顺铂分别处理肝癌细胞,利用细胞划痕实验检测肝癌细胞的迁移能力变化;设计拯救实验,探究化疗药5-氟尿嘧啶和顺铂通过诱导miR-449b表达,参与肝癌细胞迁移能力调控;软件预测结合Westernblot实验,鉴定miR-449b的功能靶基因。结果 miR-449b在肝癌患者组织中表达下调(P<0.001);5-氟尿嘧啶和顺铂诱导肝癌细胞内源性miR-449b的表达上调(P<0.001);过表达miR-449b可以抑制肝癌细胞的迁移(P<0.001);敲低miR-449b的表达可以抑制5-氟尿嘧啶和顺铂对肝癌细胞迁移能力的抑制作用(P<0.05);catenin-δ是miR-449b的直接靶基因。结论 5-氟尿嘧啶和顺铂通过诱导miR-449b的表达抑制肝癌细胞的迁移。

关键词: 关键词:miR-449b, 5-氟尿嘧啶, 顺铂, 肝细胞癌

Abstract: Objective To investigate the impact of5-Fluorouracil (5-FU) and cisplatin on micrRNA-449b (miR-449b) expression in human hepatocellular carcinoma (HCC) and elucidate the molecular mechanism of 5-FU and cisplatin inhibiting the migration of HCC cells. Methods Real-time qPCR analysis was conducted to determine the expression of miR-449b in 50 HCC tissues. Real-time PCR assay was performed to detect the expression of miR-449b in HCC cells with 5-FU and cisplatin treatment. The migration of HCC cells with the overexpression of miR-449b was determined by wound-healing assay; Rescue assay was employed to investigate the correlation between 5-FU&cisplatin, miR-449b and the migration capacity of HCC cells; The putative targets of miR-449b were predicted and validated using target prediction programs and immunoblots. Results The expression of miR-449b decreased in HCC tissues (P<0.0001). MiR-449b expression increased in HCC cells upon the treatment of 5-FU and cisplatin (P<0.001). The overexpression of miR-449b inhibited the migration of HCC cells (P<0.001). Rescue assay revealed that inhibition of miR-449b to prevent 5-FU and cisplatin induction resulted in suppressed migration in SMMC7721 cells (P<0.05). Catenin-δwasa functional target of miR-449b. Conclusions 5-FU and cisplatin inhibit the migration of HCC cells at least partly via inducing the expression of miR-449b.

Key words: Key words: miR-449b, 5-FU, cisplatin, human hepatocellular carcinoma

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