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沉默 LINC00663 通过 EBF1 下调 NR2F1 抑制膀胱癌中的炎症和血管生成。

Silencing LINC00663 inhibits inflammation and angiogenesis through downregulation of NR2F1 via EBF1 in bladder cancer.

机构信息

Department of Urology Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, P.R. China.

Medical Record Management Center, Affiliated Hospital of Qingdao University, Qingdao, Shandong, P.R. China.

出版信息

RNA Biol. 2024 Jan;21(1):9-22. doi: 10.1080/15476286.2024.2368304. Epub 2024 Jun 18.

Abstract

This study is to elucidate the effect of the LINC00663/EBF1/NR2F1 axis on inflammation and angiogenesis in bladder cancer (BC) and related molecular mechanisms. After transfection, functional experiments were conducted to test cell proliferation and invasion, tube formation ability, and content of inflammatory factors, Snail, E-cadherin, and VEGFA. Meanwhile, the relationships among LINC00663, EBF1, and NR2F1 were predicted and verified. In addition, xenograft experiments in nude mice were performed to observe the oncogenicity of 5637 BC cells . In BC tissues and cells, LINC00663 and NR2F1 were upregulated. Silencing NR2F1 or LINC00663 repressed cell proliferation and invasion, weakened vascular mimicry , decreased inflammatory factor, Snail, and VEGFA levels, and increased expression of E-cadherin. LINC00663 positively regulated NR2F1 expression through EBF1. Additionally, experiments showed that NR2F1 upregulation reversed the suppression effects of LINC00663 silencing on tumour growth, inflammation, and angiogenesis. Silencing LINC00663 decreased NR2F1 expression by mediating EBF1, thereby inhibiting BC inflammation and angiogenesis.

摘要

本研究旨在阐明 LINC00663/EBF1/NR2F1 轴在膀胱癌 (BC) 中的炎症和血管生成中的作用及其相关分子机制。转染后,通过功能实验检测细胞增殖和侵袭、管形成能力以及炎症因子、Snail、E-cadherin 和 VEGFA 的含量。同时,预测并验证了 LINC00663、EBF1 和 NR2F1 之间的关系。此外,还进行了裸鼠异种移植实验以观察 5637 BC 细胞的致癌性。在 BC 组织和细胞中,LINC00663 和 NR2F1 上调。沉默 NR2F1 或 LINC00663 抑制细胞增殖和侵袭,减弱血管模拟,降低炎症因子、Snail 和 VEGFA 水平,并增加 E-cadherin 的表达。LINC00663 通过 EBF1 正向调节 NR2F1 的表达。此外,实验表明 NR2F1 的上调逆转了 LINC00663 沉默对肿瘤生长、炎症和血管生成的抑制作用。沉默 LINC00663 通过调节 EBF1 降低 NR2F1 表达,从而抑制 BC 的炎症和血管生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e6/11188801/b985c3e59324/KRNB_A_2368304_F0001_OC.jpg

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