ANKRD1通过介导上皮细胞间充质转化促进肝细胞肝癌增殖与转移
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南京医科大学附属第一临床医院

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国家自然科学基金项目(面上项目,重点项目,重大项目)


ANKRD1 promotes proliferation and metastasis of hepatocellular carcinoma by activating epithelial mesenchymal transition pathway
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    摘要:

    目的:探究ANKRD1在肝细胞肝癌(hepatocellular carcinoma, HCC)中的表达情况以及研究ANKRD1促进HCC增殖和转移功能和机制。方法:通过qRT-PCR(Quantitative real-time PCR, qRT-PCR)与Western Blot检测ANKRD1在肝细胞肝癌及癌旁组织中的相对表达量,临床数据分析ANKRD1与HCC患者临床资料的相关性。利用慢病毒转染将肝癌细胞系中的ANKRD1敲低或过表达,通过cck-8(Cell counting kit-8, cck-8)、划痕、Transwell、EdU(5-Ethynyl-20-deoxyuridine, EdU)以及裸鼠皮下成瘤实验在体内体外检测ANKRD1对肝癌细胞增殖与迁移功能的影响。Western Blot技术检测ANKRD1对HCC细胞上皮细胞-间充质转化(epithelial-mesenchymal transition, EMT)的调控作用。结果:ANKRD1在肝癌细胞中明显表达上调,过表达ANKRD1可以促进肝癌细胞增殖、迁移、侵袭,而ANKRD1敲低则会抑制肝癌细胞的增殖与迁移,Western Blot与皮下瘤免疫组化实验表明ANKRD1可以促进HCC细胞EMT通路激活。结论:ANKRD1在肝癌细胞中表达上调并通过调控EMT通路促进HCC细胞增殖与迁移,ANKRD1可能成为肝癌治疗的新靶点。

    Abstract:

    Objective: This study aims to explore the expression of ANKRD1 in hepatocellular carcinoma and to investigate the function and mechanism of ANKRD1 in promoting the proliferation and metastasis of HCC. Methods: The relative expression of ANKRD1 in hepatocellular carcinoma and adjacent tissues was detected by qRT-PCR and western blot. Clinicopathological analysis was used to assess the association of ANKRD1 with the pathology and prognosis of HCC patients. ANKRD1 was knocked down or overexpressed in HCC cell lines by lentiviral transfection. The effects of ANKRD1 on the proliferation and migration of HCC cells were detected by cck8 assay, wound healing assay, transwell assay, EdU assay in vitro and subcutaneous tumor model in vivo. The activity of epithelial-mesenchymal transition (EMT) pathway was examined by western blot. Results: ANKRD1 was upregulated in HCC. Overexpression of ANKRD1 promoted the proliferation, migration and invasion of HCC cells and knockdown of ANKRD1 inhibited the proliferation and migration of HCC cells. Western blot experiments showed that ANKRD1 could activate EMT pathway. Conclusion: ANKRD1 is upregulated in HCC and promotes the proliferation and migration of HCC cells by regulating the EMT pathway. Our study provides a potential therapeutic target and biomarker for HCC.

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  • 收稿日期:2022-07-28
  • 最后修改日期:2022-12-06
  • 录用日期:2023-04-17
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