BOC targets SMO to regulate the Hedgehog pathway and promote proliferation, migration, and invasion of glioma cells

IF 3.5 3区 医学 Q2 NEUROSCIENCES Brain Research Bulletin Pub Date : 2024-07-30 DOI:10.1016/j.brainresbull.2024.111037
Shichao Wang , Yanhai Wang , Lingfang Hao , Bo Chen , Jiawei Zhang , Xia Li , Junwei Cao , Bin Liu
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Abstract

The purpose of this study was to investigate the effects of BOC on glioblastoma cells and its underlying mechanisms. In vitro, BOC-knockdown was performed in glioma cell lines. CCK-8 and Transwell were used to assess the impact of BOC on the viability, invasion, and migration of gliobma cells. RNA-seq technology was employed to analyze the differential gene expression between BOC-knockdown glioma cells and the control group, and qRT-PCR was used to validate the expression of downstream differential genes. SMO-overexpression was performed to investigate the effects of SMO on glioma cells. A BOC-knockdown mouse subcutaneous tumor model was to verify the effects of BOC on mouse tumors. Tissue microarray technology was used to detect the expression of BOC and SMO in samples of normal human brain tissue and glioma tissue. In vitro, BOC-knockdown inhibited the viability, invasion, and migration of glioma cells, as well as downregulated the expression of downstream differential genes SMO, EGFR, HRAS, and MRAS. Conversely, SMO-overexpression upregulated the viability, invasion, and migration abilities of BOC-knockdown cells. In vivo, BOC-knockdown suppressed tumor growth in mice and downregulated the expression of downstream differential genes SMO, EGFR, HRAS, and MRAS. Tissue microarray results showed that both BOC and SMO were highly expressed in glioma tissues. BOC is aberrantly overexpressed in glioma patients and promotes glioma development. Mechanistically, BOC activates the Hedgehog (Hh) and RAS signaling pathways by upregulating the expression of SMO, EGFR, HRAS, and MRAS, thereby facilitating the Proliferation, invasion and migration of glioma cells.

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BOC 以 SMO 为靶点调控刺猬蛋白通路,促进胶质瘤细胞的增殖、迁移和侵袭
本研究旨在探讨 BOC 对胶质母细胞瘤细胞的影响及其内在机制。在体外,对胶质瘤细胞系进行了 BOC 敲除。CCK-8和Transwell用于评估BOC对胶质母细胞瘤细胞活力、侵袭和迁移的影响。利用 RNA-seq 技术分析 BOC 敲除胶质瘤细胞与对照组之间的差异基因表达,并利用 qRT-PCR 验证下游差异基因的表达。进行SMO过表达以研究SMO对胶质瘤细胞的影响。BOC 敲除小鼠皮下肿瘤模型是为了验证 BOC 对小鼠肿瘤的影响。组织芯片技术用于检测正常人脑组织和胶质瘤组织样本中 BOC 和 SMO 的表达。在体外,敲除 BOC 可抑制胶质瘤细胞的活力、侵袭和迁移,并下调下游差异基因 SMO、表皮生长因子受体、HRAS 和 MRAS 的表达。相反,SMO的高表达则会上调BOC敲除细胞的活力、侵袭和迁移能力。在体内,BOC敲除抑制了小鼠的肿瘤生长,并下调了下游差异基因SMO、表皮生长因子受体、HRAS和MRAS的表达。组织芯片结果显示,BOC 和 SMO 在胶质瘤组织中均高表达。BOC在胶质瘤患者中异常过表达,并促进胶质瘤的发展。从机制上讲,BOC通过上调SMO、表皮生长因子受体、HRAS和MRAS的表达,激活刺猬(Hh)和RAS信号通路,从而促进胶质瘤细胞的增殖、侵袭和迁移。
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来源期刊
Brain Research Bulletin
Brain Research Bulletin 医学-神经科学
CiteScore
6.90
自引率
2.60%
发文量
253
审稿时长
67 days
期刊介绍: The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.
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