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miR-570 抑制肝癌的增殖、血管生成和免疫逃逸。

miR-570 Inhibits Proliferation, Angiogenesis, and Immune Escape of Hepatocellular Carcinoma.

机构信息

1 Department of Traditional Chinese Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute , Guangzhou, Guangdong 510080, People's Republic of China .

2 The Research Center of Integrative Medical, School of Basic Medicine, Guangzhou University of Chinese Medicine , Guangzhou, Guangdong 510405, People's Republic of China .

出版信息

Cancer Biother Radiopharm. 2018 Aug;33(6):252-257. doi: 10.1089/cbr.2017.2389. Epub 2018 Jun 6.

DOI:10.1089/cbr.2017.2389
PMID:29874097
Abstract

Hepatocellular carcinoma (HCC) is one common malignancy. The authors previously demonstrated that miR-570 regulates the development of HCC. This study detected the effect of miR-570 on cell apoptosis, angiogenesis, T cell activation, and proliferation in a tumorigenicity assay in nude mice. miR-570 mimics and negative control (NC) were transfected into SMMC7721 cells, and then, the cells were subcutaneously injected in the right flank in nude mice. Six weeks later, the dissected tumors and peripheral blood were collected. Tumor weight and volume were measured, and expression of miR-570 and apoptosis-related gene Bax/Bcl-2 was detected by quantitative real-time polymerase chain reaction. Hematoxylin and eosin, immunohistochemistry of CD31 and vascular endothelial growth factor (VEGF), TUNEL assay, and flow cytometry detection of CD4 and CD8 in peripheral blood were performed. miR-570 mimics suppressed tumor growth compared with the NC, with decreases in tumor weight and tumor volume. Very few CD31 and VEGF were found in tumor sections in miR-570 mimics group. Bax level was significantly increased, while Bcl-2 level was significantly downregulated. Significant lower ratio of CD3CD4 T cells and higher ratio of CD8IFN-γ T cells were found in peripheral blood and tumor tissues in miR-570 mimics than NC. Collectively, miR-570 plays an important role in the proliferation, angiogenesis, and immune escape of HCC, which might be potential diagnostic and predictive biomarkers.

摘要

肝细胞癌(HCC)是一种常见的恶性肿瘤。作者先前证明 miR-570 调节 HCC 的发展。本研究在裸鼠致瘤性试验中检测了 miR-570 对细胞凋亡、血管生成、T 细胞激活和增殖的影响。将 miR-570 模拟物和阴性对照(NC)转染到 SMMC7721 细胞中,然后将细胞皮下注射到裸鼠的右侧肋部。6 周后,采集切除的肿瘤和外周血。测量肿瘤重量和体积,并通过实时定量聚合酶链反应检测 miR-570 和凋亡相关基因 Bax/Bcl-2 的表达。进行苏木精和伊红、CD31 和血管内皮生长因子(VEGF)的免疫组织化学、TUNEL 检测以及外周血 CD4 和 CD8 的流式细胞术检测。与 NC 相比,miR-570 模拟物抑制了肿瘤生长,肿瘤重量和体积均减小。miR-570 模拟物组肿瘤切片中发现的 CD31 和 VEGF 非常少。Bax 水平显著升高,而 Bcl-2 水平显著下调。与 NC 相比,miR-570 模拟物组外周血和肿瘤组织中 CD3CD4 T 细胞的比例明显降低,CD8IFN-γ T 细胞的比例明显升高。总之,miR-570 在 HCC 的增殖、血管生成和免疫逃逸中发挥重要作用,可能是潜在的诊断和预测生物标志物。

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