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[1]赵文荧,于 林.GATAD1通过调控TGF-β信号通路促进胶质瘤细胞侵袭[J].天津医科大学学报,2024,30(02):116-121.[doi:10.20135/j.issn.1006-8147.2024.02.0116]
　ZHAO Wenying,YU Lin.GATAD1 promotes the invasion of glioma cells by regulating TGF-β signaling pathway[J].Journal of Tianjin Medical University,2024,30(02):116-121.[doi:10.20135/j.issn.1006-8147.2024.02.0116]
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GATAD1通过调控TGF-β信号通路促进胶质瘤细胞侵袭(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
30卷
期数:
2024年02期
页码:
116-121
栏目:
肿瘤疾病专题
出版日期:
2024-03-20

文章信息/Info

Title:
GATAD1 promotes the invasion of glioma cells by regulating TGF-β signaling pathway
文章编号:
1006-8147（2024）02-0116-06
作者:
赵文荧; 于 林
（天津医科大学基础医学院生物化学与分子生物学系，天津 300070）
Author(s):
ZHAO Wenying; YU Lin
（Department of Biochemistry and Molecular Biology，School of Basic Medical Sciences，Tianjin Medical University，Tianjin 300070，China）
关键词:
GATAD1; 胶质瘤; TGF-β信号通路; 侵袭
Keywords:
GATAD1;  glioma;  TGF-β signaling pathway;  invasion
分类号:
R739.4
DOI:
10.20135/j.issn.1006-8147.2024.02.0116
文献标志码:
A
摘要:
目的：探究GATA锌指结构域包含体1（GATAD1）影响胶质瘤细胞侵袭的分子机制。方法：对中国脑胶质瘤基因组图谱（CGGA）数据库进行GSEA分析，初步筛选GATAD1下游信号通路；在胶质瘤细胞系U87 MG中构建稳定敲低GATAD1的细胞株；通过qPCR检测GATAD1敲低后，其下游信号通路相关基因mRNA水平。结果：对CGGA数据库分析发现，GATAD1高表达与转化生长因子（TGF）-β信号通路显著相关（P＜0.05）。划痕实验结果显示，使用TGF-β1处理的对照组胶质瘤细胞愈合面积为（2.464±0.261） mm2，与未使用TGF-β1处理的对照组（1.456±0.542） mm2相比，其迁移能力明显增强（F=30.59，P＜0.01）；使用TGF-β1处理的敲低组细胞愈合面积分别为（0.541±0.058） mm2、（0.604±0.012） mm2，与未使用TGF-β1处理的敲低组[（0.492±0.063） mm2、（0.465±0.039） mm2]相比，其迁移能力无显著变化（F=30.59，P=0.999 9、0.981 6）；与TGF-β1处理的对照组相比，TGF-β1处理的敲低组细胞迁移能力显著下降（F=30.59，P＜0.000 1）。Transwell实验结果表明，使用TGF-β1处理的对照组胶质瘤细胞，穿过小室细胞数为（167.80±22.65）个，与未使用TGF-β1处理的对照组[（121.8±9.55）个]相比，其侵袭能力明显增强（F=186.6，P＜0.001）；使用TGF-β1处理的敲低组细胞穿过小室细胞数分别为（18.20±5.54）个、（16.60±7.54）个，与未使用TGF-β1处理的敲低组 [（12.80±4.66）个、（14.00±6.25）个]相比，其侵袭能力无显著变化（F=186.6，P=0.971 3、0.999 0）；与TGF-β1处理的对照组相比，TGF-β1处理的敲低组细胞侵袭能力显著下降（F=186.6，P＜0.000 1）。Q-PCR结果发现，敲低GATAD1后，TGF-β信号通路相关基因Smad2、Smad3、TGFBR1、TGFBR2、N-cadherin的mRNA水平均下降（t=18.80、12.46、73.44、54.75、44.21，均P＜0.001）。结论：GATAD1通过调控TGF-β信号通路，促进胶质瘤细胞的侵袭。
Abstract:
Objective：To explore the molecular mechanism of GATA zinc finger domain containing 1（GATAD1）on the invasion of glioma cell. Methods：GSEA analysis was performed on the Chinese Glioma Genome Atlas（CGGA）database，and the downstream signaling pathways of GATAD1 were initially screened. Stable GATAD1 knockdown strain was constructed in glioma cell lines U87 MG. Q-PCR was used to detect the effect of GATAD1 knockdown on mRNA levels of genes related to its downstream signaling pathway. Results：Analysis of CGGA database showed that the high expression of GATAD1 was significantly correlated with transforming growth factor（TGF）-β signaling pathway（P＜0.05）. Wound healing assay results showed that the healing area of glioma cells in the control group treated with TGF-β1 was（2.464±0.261） mm2，and the migration ability was significantly enhanced（F=30.59，P＜0.01） compared with the control group treated without TGF-β1[（1.456±0.542） mm2]. The healing areas of the knockdown group treated with TGF-β1 were（0.541±0.058） mm2 and（0.604±0.012） mm2，and there was no significant change in migration ability（F=30.59， P=0.999 9，0.981 6，respectively） compared with the knockdown group treated without TGF-β1[（0.492±0.063） mm2 and （0.465±0.039） mm2]. Compared with the control group treated with TGF-β1，the migration ability of the knockdown group treated with TGF-β1 was significantly decreased（both F=30.59，P＜0.000 1）. The results of Transwell showed that the number of glioma cells passing through the compartment of the control group treated with TGF-β1 was 167.8±22.65，and the invasion ability was significantly enhanced（F=186.6， P＜0.001） compared with the control group treated without TGF-β1（121.8±9.55）. In the knockdown group treated with TGF-β1，the number of cells passing through the compartment were 18.20±5.54 and 16.60±7.54，and there was no significant change in the invasion ability（F=186.6，P=0.9713，0.999 0，respectively） compared with the knockdown group treated without TGF-β1（12.80±4.66 and 14.00±6.25）. Compared with the control group treated with TGF-β1，the migration ability of the knockdown group treated with TGF-β1 was significantly decreased（F=186.6，P＜0.000 1）. Q-PCR results showed that mRNA levels of TGF-β signaling pathway related genes Smad2，Smad3，TGFBR1，TGFBR2 and N-cadherin were decreased after GATAD1 knockdown（t=18.80，12.46，73.44，54.75 and 44.21，respectively，all P＜0.001）. Conclusion：GATAD1 promotes the invasion of glioma cells by regulating TGF-β signaling pathway.

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备注/Memo

备注/Memo:
作者简介 赵文荧（1997-），女，硕士在读，研究方向：肿瘤转移相关分子生物学；通信作者：于林，E-mail：onoblivion@tmu.edu.cn。
更新日期/Last Update: 2024-03-20