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B7-H6 通过靶向 c-MYC 激活促进小脑细胞瘤迁移和侵袭增强 F- 肌动蛋白重排。

B7-H6 enhances F-actin rearrangement by targeting c-MYC activation to promote medulloblastoma migration and invasion.

机构信息

School of Medicine, Chongqing University, Chongqing, China.

Department of Pathology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, China.

出版信息

Med Oncol. 2023 Jan 24;40(3):85. doi: 10.1007/s12032-023-01947-5.

DOI:10.1007/s12032-023-01947-5
PMID:36692844
Abstract

Medulloblastoma (MB) is children's most common primary malignant primitive neuro-ectodermal tumor. Group 3 MB showed a higher propensity to metastasis, which is molecularly characterized by c-MYC gene amplification. The activation of c-MYC promotes the remodeling of the F-actin cytoskeleton to enhance metastasis. The B7 homologue 6 (B7-H6) is associated with the manifold essential hallmarks of tumorigenesis. In this study, we will explore whether B7-H6 regulates the reorganization of F-actin by elevating the c-MYC expression to promote metastasis. The Daoy cell line was used to act as the cell model of medulloblastoma. Small interfering RNA and the plasmid were used to downregulate and upregulate the expression of B7-H6 in Daoy cells. Transwell assays with/without the matrigel matrix were used to detect migration and invasion of Daoy cells. Western blots were used to detect the expression of related proteins. Immunofluorescence staining was used to observe the impact of B7-H6 on the c-MYC /F-actin axis. B7-H6 improved migration and invasion in the Daoy cell line. B7-H6 enhanced the rearrangement of F-actin and activated the expression of MMP-9 and MMP-2. B7-H6 promoted the remodeling of F-actin by targeting c-MYC activation to reinforce migration and invasion. B7-H6 acts as a promoter of migration and invasion in medulloblastoma by activating the c-MYC /F-actin axis.

摘要

髓母细胞瘤(MB)是儿童最常见的原发性恶性原始神经外胚层肿瘤。第 3 组 MB 具有更高的转移倾向,其分子特征是 c-MYC 基因扩增。c-MYC 的激活促进 F-肌动蛋白细胞骨架的重塑,从而增强转移。B7 同源物 6(B7-H6)与肿瘤发生的多种基本特征有关。在这项研究中,我们将探讨 B7-H6 是否通过上调 c-MYC 表达来调节 F-肌动蛋白的重排,从而促进转移。Daoy 细胞系被用作髓母细胞瘤的细胞模型。使用小干扰 RNA 和质粒下调和上调 Daoy 细胞中 B7-H6 的表达。使用带有/不带有基质胶基质的 Transwell 测定法检测 Daoy 细胞的迁移和侵袭。使用 Western blot 检测相关蛋白的表达。免疫荧光染色观察 B7-H6 对 c-MYC/F-肌动蛋白轴的影响。B7-H6 改善了 Daoy 细胞系的迁移和侵袭。B7-H6 增强了 F-肌动蛋白的重排,并激活了 MMP-9 和 MMP-2 的表达。B7-H6 通过靶向 c-MYC 激活来重塑 F-肌动蛋白,从而增强迁移和侵袭。B7-H6 通过激活 c-MYC/F-肌动蛋白轴在髓母细胞瘤中充当迁移和侵袭的促进剂。

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