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微小 RNA-218 通过靶向 GAB2 抑制人肾细胞癌的肿瘤血管生成。

MicroRNA‑218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2.

机构信息

Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Department of Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

出版信息

Oncol Rep. 2020 Nov;44(5):1961-1970. doi: 10.3892/or.2020.7759. Epub 2020 Sep 8.

DOI:10.3892/or.2020.7759
PMID:32901879
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7551166/
Abstract

Renal cell carcinoma (RCC) is one of the most common malignant cancers in the adult urinary system worldwide. Tumor angiogenesis is a critical process during cancer progression, as it modulates carcinogenesis and metastasis. In recent years, microRNA‑218 (miR‑218) has been confirmed to play a crucial role in tumor suppression. However, the role of miR‑218 in RCC angiogenesis remains unclear. In the present study, it was found that the expression of miR‑218 was decreased in RCC tumor tissues and cell lines as detected by real‑time PCR analysis. Tube formation assays and migration assays also confirmed that miR‑218 inhibited the interaction between RCC cells and vascular endothelial cells by suppressing proangiogenic factor vascular endothelial growth factor A (VEGFA) in RCC cells. miR‑218 also repressed the subcutaneous tumorigenesis of RCC cells in nude mice, and the corneal angiogenesis in rabbit eyes. The underlying molecular mechanism was elucidated; miR‑218 targets GRB2‑associated binding protein 2 (GAB2), thereby inhibiting the PI3K/AKT/mTOR/VEGFA pathway. These results provide new insights into the mechanism of RCC carcinogenesis and progression, suggesting that miRNA‑218 may be a therapeutic target for the treatment of RCC.

摘要

肾细胞癌（RCC）是全球成人泌尿系统中最常见的恶性肿瘤之一。肿瘤血管生成是癌症进展过程中的一个关键过程，它调节着癌变和转移。近年来，miR-218（miR-218）已被证实在肿瘤抑制中发挥着关键作用。然而，miR-218 在 RCC 血管生成中的作用尚不清楚。在本研究中，通过实时 PCR 分析发现，miR-218 在 RCC 肿瘤组织和细胞系中的表达降低。管形成试验和迁移试验也证实，miR-218 通过抑制 RCC 细胞中的促血管生成因子血管内皮生长因子 A（VEGFA）抑制了 RCC 细胞与血管内皮细胞的相互作用。miR-218 还抑制了裸鼠中 RCC 细胞的皮下肿瘤发生和兔眼的角膜血管生成。阐明了潜在的分子机制；miR-218 靶向 GRB2 相关结合蛋白 2（GAB2），从而抑制了 PI3K/AKT/mTOR/VEGFA 通路。这些结果为 RCC 发生和进展的机制提供了新的见解，表明 miRNA-218 可能是治疗 RCC 的一个治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b7/7551166/e59c8283078b/OR-44-05-1961-g06.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b7/7551166/e59c8283078b/OR-44-05-1961-g06.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b7/7551166/986c0d522571/OR-44-05-1961-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b7/7551166/6d8a4baa4f11/OR-44-05-1961-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7b7/7551166/a503fac53512/OR-44-05-1961-g03.jpg
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