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Axin1通过靶向miR-650抑制肝癌细胞的增殖、侵袭、迁移和上皮-间质转化。

Axin1 inhibits proliferation, invasion, migration and EMT of hepatocellular carcinoma by targeting miR-650.

作者信息

Qin Ancheng, Wu Jianwu, Zhai Min, Lu Yijie, Huang Bo, Lu Xingsheng, Jiang Xinwei, Qiao Zhiming

机构信息

Department of Hepatobiliary Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou 215002, Jiangsu, P. R. China.

出版信息

Am J Transl Res. 2020 Mar 15;12(3):1114-1122. eCollection 2020.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high mortality rate and low survival rate. This study was designed to explore a novel molecular with high sensitivity and specificity, which can be applied in early diagnosis and therapeutic evaluation of HCC. The current study aims to investigate the effect and important role of Axin1 on cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma. qRT-PCR results showed lower Axin1 expression level and higher miR-650 expression level in HCC. Luciferase reporter assay was carried out to verify the negative correlation between Axin1 and miR-650 mRNA levels. CCK-8 assay results showed that the cell proliferation ability was significantly suppressed by Axin1 overexpression in SK-HEP-1 cells. The results in wound healing assay uncovered that cell migration ability was markedly suppressed by Axin1 overexpression. The results in trans-well invasion assay showed that Axin1 overexpression caused decreased invasive ability in SK-HEP-1 cells. The WB results showed that the protein level of E-cad was significantly increased and the protein levels of N-cad, vimentin and snail were obviously reduced following Axin1 overexpression. Whereas, the suppressive effects on cell proliferation, migration, invasion and EMT caused by Axin1 overexpression were abolished by miR-650 mimic. All the results in the current study confirmed the truth that Axin1 overexpression could suppress cell proliferation, migration, invasion and EMT by downregulating miR-650 expression.

摘要

肝细胞癌(HCC)是最常见的恶性肿瘤之一,死亡率高,生存率低。本研究旨在探索一种具有高敏感性和特异性的新型分子,可应用于HCC的早期诊断和治疗评估。当前研究旨在探讨Axin1对肝细胞癌细胞增殖、侵袭、迁移和上皮-间质转化(EMT)的作用及重要性。qRT-PCR结果显示,HCC中Axin1表达水平较低,miR-650表达水平较高。进行荧光素酶报告基因检测以验证Axin1与miR-650 mRNA水平之间的负相关。CCK-8检测结果表明,SK-HEP-1细胞中Axin1过表达显著抑制细胞增殖能力。伤口愈合检测结果表明,Axin1过表达显著抑制细胞迁移能力。Trans-well侵袭检测结果显示,Axin1过表达导致SK-HEP-1细胞侵袭能力下降。WB结果显示,Axin1过表达后,E-cad蛋白水平显著升高,N-cad、波形蛋白和蜗牛蛋白水平明显降低。然而,miR-650模拟物消除了Axin1过表达对细胞增殖、迁移、侵袭和EMT的抑制作用。本研究的所有结果证实了Axin1过表达可通过下调miR-650表达来抑制细胞增殖、迁移、侵袭和EMT这一事实。

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