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miR-145 在 U87 细胞中的过表达降低了神经胶质瘤细胞的恶性表型,并促进了体内植入后的存活。

Overexpression of miR‑145 in U87 cells reduces glioma cell malignant phenotype and promotes survival after in vivo implantation.

机构信息

Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.

Department of Hematology/Oncology, Henry Ford Hospital, Detroit, MI, USA.

出版信息

Int J Oncol. 2015 Mar;46(3):1031-8. doi: 10.3892/ijo.2014.2807. Epub 2014 Dec 23.

Abstract

In the present study, we sought to elucidate the effect of miR‑145 on glioma cell progression and its mechanisms of action. We examined the effects of miR‑145 on proliferation and invasion of U87 glioma cells and on capillary tube formation. Our data show that restoration of miR‑145 in U87 glioma cells significantly reduced their in vitro proliferation, invasion and angiogenesis. However, decreased miR‑145 expression promoted U87 glioma cell proliferation, invasion and angiogenesis, and reduced-expression of miR‑145 increased ADAM17 and EGFR expression in U87 cells. Overexpression of miR‑145 reduced ADAM17 and EGFR expression. VEGF secretion and VEGF expression were decreased by increased miR‑145 expression in U87 cells and were reversed by miR‑145 downregulation in vitro. Nude mice with intracerebral implantation of U87 overexpressing miR‑145 cells exhibited significantly reduced tumor growth and promoted survival compared with control groups. Taken together, these results suggest a role for miR‑145 as a tumor suppressor which inhibits glioma cell proliferation, invasion and angiogenesis in vitro and reduces glioma growth in vivo.

摘要

在本研究中,我们试图阐明 miR-145 对神经胶质瘤细胞进展的影响及其作用机制。我们研究了 miR-145 对 U87 神经胶质瘤细胞增殖和侵袭以及毛细血管形成的影响。我们的数据表明,在 U87 神经胶质瘤细胞中恢复 miR-145 显著降低了其体外增殖、侵袭和血管生成。然而,miR-145 表达降低促进了 U87 神经胶质瘤细胞的增殖、侵袭和血管生成,并且 miR-145 表达降低增加了 U87 细胞中 ADAM17 和 EGFR 的表达。miR-145 的过表达降低了 ADAM17 和 EGFR 的表达。miR-145 在 U87 细胞中的过表达降低了 VEGF 的分泌和表达,并且在体外通过下调 miR-145 而得到逆转。与对照组相比,颅内植入过表达 miR-145 的 U87 细胞的裸鼠显示出肿瘤生长明显减少和存活时间延长。总之,这些结果表明 miR-145 作为一种肿瘤抑制因子发挥作用,可抑制体外神经胶质瘤细胞的增殖、侵袭和血管生成,并减少体内神经胶质瘤的生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1382/4324582/e72e50ebf61a/IJO-46-03-1031-g00.jpg

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