敲除 Anoikis 相关基因 OCIAD2 可减少胶质母细胞瘤细胞株的增殖和迁移。

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Combinatorial chemistry & high throughput screening Pub Date : 2024-07-29 DOI:10.2174/0113862073305357240719070044
Danna Huang, Lu Chen, Yu Liu, Wuwei Wu, Yingying Liu, Yu Pan
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引用次数: 0

摘要

背景:胶质母细胞瘤(GBM胶质母细胞瘤(GBM)严重影响患者的生活质量。嗜酸性细胞是癌症侵袭和转移的重要机制。我们的研究重点是anoikis相关基因与GBM之间的预后关系及其对GBM细胞进展的影响:我们分别从 TCGA 和 CGGA 队列数据集中下载了 656 和 979 个 GBM 样本数据。我们从GeneCards数据库中获得了15个anoikis相关基因,随后对这些基因进行聚类,以确定与之相关的差异基因。经过LAASO筛选,5个差异基因的表达值为LASSO回归系数之和。利用TCGA训练集和CGGA验证集对anoikis评分进行了生存分析和ROC曲线分析。使用 Cox 回归分析对 GBM 的预后因素进行了分析。此外,还使用 CCK-8、菌落形成、伤口愈合和转孔试验来评估 GBM 细胞的增殖和迁移:结果:两组 GBM 患者的 5 年生存率存在显著差异。我们的分析表明,OCIAD2、FTLP3、IGFBP2 和 H19 水平高与较低的 GBM 5 年生存率相关,而 SFRP2 水平高与较高的生存率相关。单变量 Cox 分析表明,GBM 风险与 anoikis 评分和等级有关,而多变量 Cox 分析表明,GBM 风险与 anoikis 评分和年龄有关。此外,OCIAD2 在 U251MG 和 T98G 细胞中高表达。此外,沉默 OCIAD2 可抑制 GBM 细胞的增殖和迁移:结论:本研究证明了厌氧相关基因 OCIAD2 作为 GBM 预后生物标志物的潜力。此外,我们还在体外验证了 OCIAD2 可促进 GBM 细胞的进展。
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Knockdown of Anoikis-Associated Gene OCIAD2 Reduces Proliferation and Migration of Glioblastoma Cell Lines.

Background: Glioblastoma (GBM) severely disrupts the quality of life of patients. Anoikis represents a significant mechanism in cancer invasion and metastasis. Our study focused on the prognostic relationship between the anoikis-associated gene and GBM and its effect on GBM cell progression.

Methods: We downloaded 656 and 979 GBM sample data from TCGA and CGGA cohort datasets, respectively. Fifteen anoikis-associated genes were obtained from the GeneCards database and were subsequently clustered to identify differential genes associated with them. After LAASO screening, the expression values of the 5 differential genes were the sum of LASSO regression coefficients. Survival analysis and ROC curve analysis of anoikis scores were performed using the TCGA training and CGGA validation sets. The prognostic factors were analyzed using Cox regression analysis in GBM. Moreover, CCK-8, colony formation, wound healing, and transwell assay were used to evaluate GBM cell proliferation and migration.

Results: Significant differences were observed in the 5-year survival of GBM patients between the two subgroups. Then, our analysis demonstrated that high OCIAD2, FTLP3, IGFBP2, and H19 levels were associated with lower 5-year GBM survival rates, whereas high SFRP2 levels were associated with higher survival rates. Univariate Cox analysis indicated that GBM risk was linked to both anoikis score and grade, while multivariate Cox analysis indicated that GBM risk was associated with both anoikis score and age. Additionally, OCIAD2 was highly expressed in U251MG and T98G cells. Moreover, OCIAD2 silencing inhibited GBM cell proliferation and migration.

Conclusion: This study demonstrated the potential of the anoikis-associated gene OCIAD2 as a prognostic biomarker for GBM. Furthermore, we validated in vitro that OCIAD2 promoted GBM cell progression.

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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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