Ring finger protein 14 promotes proliferation, migration and invasion of hepatoma cells by inhibiting hepatocyte nuclear factor-1α

Guangxi ZHU; Wensheng WANG; Liang ZHANG; Liangzhi WEN; Dongfeng CHEN

doi:10.16016/j.1000-5404.201910077

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Ring finger protein 14 promotes proliferation, migration and invasion of hepatoma cells by inhibiting hepatocyte nuclear factor-1α

Basic Medicine | 更新时间：2026-01-09

- Ring finger protein 14 promotes proliferation, migration and invasion of hepatoma cells by inhibiting hepatocyte nuclear factor-1α
- Journal of Third Military Medical University Vol. 42, Issue 4, Pages: 375-383(2020)
- 作者机构：
  
  400042 重庆，陆军军医大学(第三军医大学)大坪医院消化内科
- 作者简介：
- 基金信息：
  
  the National Nature Science Foundation for Young Scholar of China(81802459)
- DOI：10.16016/j.1000-5404.201910077
  CLC： R341; R730.23; R735.7
- Received：14 October 2019，
  
  Revised：2019-11-02，
  
  Published：28 February 2020
- 稿件说明：
移动端阅览
Guangxi ZHU, Wensheng WANG, Liang ZHANG, et al. Ring finger protein 14 promotes proliferation, migration and invasion of hepatoma cells by inhibiting hepatocyte nuclear factor-1α[J]. Journal of Third Military Medical University, 2020, 42(4): 375-383.
DOI：

Guangxi ZHU, Wensheng WANG, Liang ZHANG, et al. Ring finger protein 14 promotes proliferation, migration and invasion of hepatoma cells by inhibiting hepatocyte nuclear factor-1α[J]. Journal of Third Military Medical University, 2020, 42(4): 375-383. DOI： 10.16016/j.1000-5404.201910077.

摘要

目的

研究环指蛋白14(ring finger protein 14，RNF14)对肝癌细胞增殖与侵袭转移能力的影响，并探讨RNF14在肝癌发生、发展中的作用机制。

方法

[利用基因表达谱交互式分析网站(Gene Expression Profiling Interactive Analysis

GEPIA；

http://gepia.cancer-pku.cn

)与Western blot实验分析正常人肝细胞与肝癌细胞间RNF14的表达差异；应用Transwell小室迁移与侵袭实验研究过表达和敲低RNF14对肝癌细胞(Hu7、7404)运动迁移能力的影响；通过CCK-8增殖实验、克隆形成实验及裸鼠皮下成瘤实验体外、体内共同验证RNF14对肝癌细胞7404增殖能力的影响；通过免疫共沉淀实验检测RNF14与肝细胞核因子1α(hepatocyte nuclear factor-1alpha，HNF1α)之间的相互作用。

结果

GEPIA与Western blot实验结果显示:RNF14在肝癌组织和肝癌细胞中的表达分别显著高于癌旁组织和正常肝细胞(

0.05)。Transwell侵袭迁移实验结果显示:过表达RNF14后，肝癌细胞Hu7的迁移与侵袭能力显著高于阴性对照组(

0.05)，同样地，敲低RNF14后，肝癌细胞7404的迁移与侵袭能力显著低于阴性对照组(

0.05)。CCK-8增殖实验、克隆形成与皮下移植瘤实验结果证明:敲低RNF14能够显著抑制肝癌细胞的增殖(

0.05)。免疫共沉淀实验结果显示:RNF14与HNF1α之间存在相互结合，且RNF14能够下调HNF1α的表达。

结论

RNF14能够通过抑制抑癌因子HNF1α的表达，增强肝癌细胞的增殖与侵袭转移能力，从而在肝癌的发生、发展中起到重要作用。

Abstract

Objective

To investigate the effects of ring finger protein 14 (RNF14) overexpression and knockdown on the proliferation and invasion of hepatoma cells and explore the mechanism by which RNF14 promote the occurrence and progression of hepatocellular carcinoma (HCC).

Methods

We investigated the expression of RNF14 in HCC and adjacent tissues using Gene Expression Profiling Interactive Analysis (GEPIA)

and examined its expression in normal human hepatocytes and hepatoma cells using Western blotting. The effects of overexpression and knockdown of RNF14 on the migration and invasion abilities of 2 hepatoma cell lines (Hu7 and 7404) were observed using Transwell chamber migration and invasion assay. The effect of RNF14 knockdown on the proliferation of hepatoma cells 7404 was verified by CCK8 proliferation assay

colony formation assay and subcutaneous xenograft tumor formation in nude mice. The interaction between RNF14 and hepatocyte nuclear factor-1α (HNF1α) was tested with co-immunoprecipitation assay.

Results

The results of GEPIA and Western blotting showed that the expression of RNF14 was significantly higher in hepatoma tissues and cells than in normal hepatic tissues and hepatocytes (

0.05). Transwell chamber invasion and migration assays showed that the migration and invasion abilities of Hu7 cells were increased significantly after overexpression of RNF14 (

0.05)

and RNF14 knockdown significantly attenuated the migration and invasion ability of hepatoma cells 7404 (

0.05). The results of CCK8 proliferation assay

colony formation and subcutaneous xenograft tumor formation in nude mice all demonstrated that RNF14 knockdown significantly inhibited the proliferation of hepatoma cells (

0.05). Co-immunoprecipitation confirmed that RNF14 could bind to HNF1α and down-regulate the expression of the latter.

Conclusion

RNF14 promotes the proliferation

migration and invasion of hepatoma cells through degrading HNF1α

and may thus play an important role in the occurrence and progression of HCC.

关键词

Keywords

references

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