PDCL3 as a prognostic factor and associated with the VEGF signaling pathway in glioma

IF 3.2 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2024-08-06 DOI:10.1002/jgm.3724
Bo Yang, Guangwei Zheng, Feng Lu
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引用次数: 0

Abstract

Background

New targeted drugs about angiogenesis could develop the treatment of glioma. We aimed to explore the role of phosducin like 3 (PDCL3) in angiogenesis of glioma.

Materials and Methods

RNA sequencing data and matched clinical data were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. To screen for the reliable genes with the filtering analyses, survival, multivariate Cox, receiver operating characteristic (ROC) curve filtration, and clinical correlation analyses were performed. The PDCL3 gene was validated by immunohistochemistry as a reliable gene for further analysis. Then we used the combined data of TCGA and Genotype-Tissue Expression from UCSC to detect the differential gene expression of PDCL3. Related signal pathways in glioma were explored by the gene set enrichment analysis and co-expression analysis. Lastly, we performed in vitro experiments to verify the gene functions and related mechanisms.

Results

The three filtering analyses and immunostaining indicated that the expression of PDCL3 in glioma tissues was higher than the normal tissues. Gene function analysis showed that PDCL3 activated the vascular endothelial growth factor (VEGF) signal pathway, and its mechanism was related to pathways in cancer, like NOD like receptor signaling pathway, the RIG-I like receptor signaling pathway and the P53 signaling pathway by MAPK/AKT in gliomas. This suggested that the proliferation, migration and invasion of glioma cells might be inhibited by the downregulation of PDCL3 in vitro, which may be related to the activation of VEGF signaling pathway.

Conclusion

We demonstrated that PDCL3 could function as an independent adverse prognostic marker in glioma. Its pro-oncogenic mechanism may be related to the VEGF signaling pathway.

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PDCL3是胶质瘤的预后因子,与血管内皮生长因子信号通路相关。
背景:有关血管生成的新靶向药物可促进胶质瘤的治疗。我们的目的是探讨类磷脂蛋白3(PDCL3)在胶质瘤血管生成中的作用:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)和中国胶质瘤基因组图谱(Chinese Glioma Genome Atlas,CGGA)数据库下载RNA测序数据和匹配的临床数据。为筛选出可靠的基因,进行了生存分析、多变量 Cox 分析、接收者操作特征曲线(ROC)筛选分析和临床相关性分析。经免疫组化验证,PDCL3基因是进一步分析的可靠基因。然后,我们利用 TCGA 和 UCSC 的基因型-组织表达联合数据检测了 PDCL3 的差异基因表达。通过基因组富集分析和共表达分析,我们探索了胶质瘤中的相关信号通路。最后,我们进行了体外实验来验证基因的功能和相关机制:结果:三种筛选分析和免疫染色表明,PDCL3在胶质瘤组织中的表达高于正常组织。基因功能分析表明,PDCL3能激活血管内皮生长因子(VEGF)信号通路,其机制与肿瘤中的通路有关,如胶质瘤中的NOD样受体信号通路、RIG-I样受体信号通路和MAPK/AKT的P53信号通路。这表明,体外下调PDCL3可抑制胶质瘤细胞的增殖、迁移和侵袭,这可能与血管内皮生长因子信号通路的激活有关:结论:我们的研究表明,PDCL3可作为胶质瘤独立的不良预后标志物。结论:我们的研究表明,PDCL3可作为胶质瘤的独立不良预后标志物,其促癌机制可能与血管内皮生长因子信号通路有关。
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来源期刊
Journal of Gene Medicine
Journal of Gene Medicine 医学-生物工程与应用微生物
CiteScore
6.40
自引率
0.00%
发文量
80
审稿时长
6-12 weeks
期刊介绍: The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.
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