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上调 通过抑制 PTEN 表达促进肝癌转移。

Up-regulated enhances hepatocarcinoma metastasis by repressing PTEN expression.

机构信息

Department of Laboratory Medicine, Huaihe Hospital of Henan University, Kaifeng 475000, Henan, China.

Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan, China.

出版信息

Biosci Rep. 2017 Dec 15;37(6). doi: 10.1042/BSR20170837. Print 2017 Dec 22.

Abstract

It has been shown that may play an important role in the metastasis of hepatocarcinoma. The present study is to explore the influence of on hepatocarcinoma proliferation and metastasis, and the related molecular mechanism. The levels of in the serum and tissues of patients with metastatic or non-metastatic hepatocarcinoma or normal people were determined by quantitative reverse transcription-PCR (qRT-PCR). The proliferation, invasion, and cloning of hepatocarcinoma cell lines SMMC-7721 after transfection with mimic or inhibitor were determined. Luciferase reported assay was used to explore the relationship between and phosphatase and tensin homologue (PTEN). Then, the protein expression of PTEN, p-Akt (S473), p-Akt (T308), Akt, p-mTOR, mTOR, p-4E-BP1, 4E-BP1, p-S6K, and S6K in SMMC-7721 cells were also determined by Western blotting. The expression of in patients with metastatic hepatocarcinoma was significantly higher than the non-metastatic hepatocarcinoma. Overexpression of promoted the proliferation, invasion, and cloning of SMMC-7721 cells. Luciferase reported assay showed could directly target at 3'-UTR of PTEN. Overexpression of significantly reduced the expression of PTEN, and enhanced phosphorylation of Akt, mTOR, S6K, and 4E-BP1. In conclusion, the expression of was related to the proliferation and metastasis of hepatocarcinoma, which may be partly because of the activation of AKT/mTOR pathway through targetting PTEN.

摘要

已经表明,可能在肝癌转移中发挥重要作用。本研究旨在探讨对肝癌增殖和转移的影响,以及相关的分子机制。通过定量逆转录聚合酶链反应(qRT-PCR)测定转移性或非转移性肝癌患者或正常人血清和组织中水平。转染模拟物或抑制剂后肝癌细胞系 SMMC-7721 的增殖、侵袭和克隆能力。荧光素酶报告试验用于探讨与磷酸酶和张力蛋白同源物(PTEN)的关系。然后,通过 Western blot 测定 SMMC-7721 细胞中 PTEN、p-Akt(S473)、p-Akt(T308)、Akt、p-mTOR、mTOR、p-4E-BP1、4E-BP1、p-S6K 和 S6K 的蛋白表达。转移性肝癌患者中的表达明显高于非转移性肝癌。过表达促进了 SMMC-7721 细胞的增殖、侵袭和克隆。荧光素酶报告试验表明可以直接靶向 PTEN 的 3'-UTR。过表达显著降低了 PTEN 的表达,并增强了 Akt、mTOR、S6K 和 4E-BP1 的磷酸化。总之,的表达与肝癌的增殖和转移有关,这可能部分是因为通过靶向 PTEN 激活了 AKT/mTOR 通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca2e/6435470/9bcc58621c3c/bsr-37-bsr20170837-g1.jpg

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