巫佳翠,刘 敏,高洪泉.miR-421通过抑制PDCD4发挥促进肝癌的作用[J].肿瘤学杂志,2019,25(10):849-857.
miR-421通过抑制PDCD4发挥促进肝癌的作用
MiR-421 Plays a Role in Promoting Liver Cancer by Inhibiting PDCD4
投稿时间:2019-01-29  
DOI:10.11735/j.issn.1671-170X.2019.10.B001
中文关键词:  肝肿瘤  miR-421  程序性细胞死亡-4
英文关键词:liver cancer  miR-421  PDCD4
基金项目:
作者单位
巫佳翠 厦门医学院基础医学部解剖教研室 
刘 敏 厦门医学院基础医学部解剖教研室 
高洪泉 厦门医学院基础医学部解剖教研室 
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中文摘要:
      摘 要:[目的] 分析miR-421通过靶向调控PDCD4的表达水平在肝癌的发生及发展中的作用。[方法] 通过构建肝癌裸鼠移植瘤模型检测miR-421对移植瘤生长的影响;检测miR-421在肝癌细胞株及肿瘤组织中的表达量及其过表达在高/低侵袭转移能力肝癌细胞模型中对侵袭能力的影响;TargetScan预测miR-421的潜在靶基因,并采用双荧光素酶报告基因法验证,qRT-PCR和Western blot检测miR-421对靶基因的调控作用;检测PDCD4在肝癌细胞株肿和肿瘤组织中的表达;CCK8、流式细胞法、Tranwell和细胞划痕检测miR-421与靶基因对肝癌细胞增殖、周期、侵袭和迁移的调控。[结果] 肝癌裸鼠移植瘤模型中过表达miR-421可促进肝癌细胞的增殖及肿瘤的生长。miR-421在肝癌细胞及肿瘤组织中均呈高表达并且上调其表达可提高肝癌细胞的侵袭能力。PDCD4受miR-421的靶向调控,并在肝癌细胞及肝癌肿瘤组织中呈低表达。miR-421过表达可促进肝癌细胞的增殖、侵袭、迁移及S期阻滞,但PDCD4可逆转这种促进效果。[结论] miR-421通过负性调控靶基因PDCD4在肝癌中扮演促癌基因的角色。
英文摘要:
      Abstract:[Objective] To analyze the role of miR-421 in the occurrence and development of liver cancer by targeting the regulation of PDCD4 expression level.[Methods] The effect of miR-421 on the growth of transplanted tumor was detected by constructing the xenograft tumor model of nude mice with liver cancer,and the expression level of miR-421 in liver cancer cell lines and tumor tissues and the effect of overexpression on the invasion ability in the liver cancer cell model with high/low invasion and metastasis ability was detected. The potential target gene of miR-421was predicted by TargetScan,and which was verified by double luciferase reporter gene method,regulatory effect of miR-421 on the target gene was detected by qRT-PCR and Western blot ,and PDCD4 expression in liver cancer cell lines and tumor tissues was detected. The regulation of miR-421 and target genes on the proliferation,cycle,invasion,and migration of HCC cells was detected by CCK8,flow cytometry,Tranwell and cell scratch. [Results] It was found that overexpression of miR-421 in the transplanted tumor model of nude mice with liver cancer promoted the proliferation and tumor growth of liver cancer cells.miR-421 was highly expressed in both liver cancer cells and tumor tissues,and this up-regulated expression could improved the invasion ability of liver cancer cells.PDCD4 was regulated by miR-421,and was low expressed in liver cancer cells and tumor tissues. miR-421 overexpression could promoted the proliferation,invasion,migration and s-phase arrest of HCC cells,but PDCD4 could reversed this effect.[Conclusion] MiR-421 plays the role of oncogene in liver cancer by negatively regulating the target gene PDCD4.
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