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PA2G4P4假基因在膀胱癌肿瘤发生中的作用。

Role of PA2G4P4 pseudogene in bladder cancer tumorigenesis.

作者信息

Pisapia Laura, Terreri Sara, Barba Pasquale, Mastroianni Marianna, Donnini Maria, Mercadante Vincenzo, Palmieri Alessandro, Verze Paolo, Mirone Vincenzo, Altieri Vincenzo, Califano Gianluigi, Liguori Giovanna Lucia, Strazzullo Maria, Cimmino Amelia, Del Pozzo Giovanna

机构信息

Institute of Genetics and Biophysics, CNR, 80131 Naples, Italy.

B Cell Pathophysiology Unit, IRCCS Bambino Gesù Children's Hospital, 00146 Rome, Italy.

出版信息

Biology (Basel). 2020 Mar 31;9(4):66. doi: 10.3390/biology9040066.

Abstract

BACKGROUND

Many pseudogenes possess biological activities and play important roles in the pathogenesis of various types of cancer including bladder cancer (BlCa), which still lacks suitable molecular biomarkers. Recently, pseudogenes were found to be significantly enriched in a pan-cancer classification based on the Cancer Genome Atlas gene expression data. Among them, the top-ranking pseudogene was the proliferation-associated 2G4 pseudogene 4 ).

METHODS

Genomic and transcript features of were determined by GeneBank database analysis followed by 5' RACE experiments. Therefore, we conducted a retrospective molecular study on a cohort of 45 patients of BlCa. expression was measured by RT-qPCR, whereas transcript distribution was analyzed by in situ hybridization on both normal and cancerous histological sections and compared to the immunolocalization of its parental protein. Finally, we tested the effects of depletion on proliferation, migration, and death of BlCa cells.

RESULTS

We showed for the first time overexpression in BlCa tissues and in cell lines. distribution strictly overlaps PA2G4/EBP1 protein localization. Moreover, we showed that knockdown affects both proliferation and migration of BlCa cells, highlighting its potential oncogenic role.

CONCLUSIONS

may play a functional role as an oncogene in BlCa development, suggesting it as a good candidate for future investigation and new clinical applications.

摘要

背景

许多假基因具有生物学活性,并在包括膀胱癌(BlCa)在内的各种癌症的发病机制中发挥重要作用,而膀胱癌仍缺乏合适的分子生物标志物。最近,基于癌症基因组图谱基因表达数据发现假基因在泛癌分类中显著富集。其中,排名靠前的假基因是增殖相关2G4假基因4。

方法

通过基因库数据库分析和5' RACE实验确定了[假基因名称]的基因组和转录特征。因此,我们对45例膀胱癌患者进行了回顾性分子研究。通过RT-qPCR测量[假基因名称]的表达,而通过原位杂交分析[假基因名称]转录本在正常和癌组织切片中的分布,并与其亲本[蛋白质名称]蛋白的免疫定位进行比较。最后,我们测试了[假基因名称]缺失对膀胱癌细胞增殖、迁移和死亡的影响。

结果

我们首次在膀胱癌组织和细胞系中显示了[假基因名称]的过表达。[假基因名称]的分布与PA2G4/EBP1蛋白定位严格重叠。此外,我们表明[假基因名称]敲低影响膀胱癌细胞的增殖和迁移,突出了其潜在的致癌作用。

结论

[假基因名称]可能在膀胱癌发生发展中作为癌基因发挥功能作用,表明它是未来研究和新临床应用的良好候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc9b/7235711/a7244a63b387/biology-09-00066-g001.jpg

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