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乳腺癌亚型中乙酰肝素酶相关基因的计算机模拟研究

In silico investigation of heparanase-correlated genes in breast cancer subtypes.

作者信息

Melo Carina Mucciolo, Prado Henrique Pereira, Attie Gabriela Araújo, Ruiz Daniel Lacaz, Girão Manoel João Batista Castello, Pinhal Maria Aparecida da Silva

机构信息

Faculdade de Medicina do ABC, Santo André, SP, Brazil.

Universidade Federal de São Paulo, São Paulo, SP, Brazil.

出版信息

Einstein (Sao Paulo). 2020 Oct 7;18:eAO5447. doi: 10.31744/einstein_journal/2020AO5447. eCollection 2020.

Abstract

OBJECTIVE

To investigate the possible genes that may be related to the mechanisms that modulate heparanase-1.

METHODS

The analysis was conducted at Universidade Federal de São Paulo, on the data provided by: The Cancer Genome Atlas, University of California Santa Cruz Genome Browser, Kyoto Encyclopedia of Genes and Genomes Pathway Database, Database for Annotation, Visualization and Integrated Discovery Bioinformatics Database and the softwares cBioPortal and Ingenuity Pathway Analysis.

RESULTS

Using messenger RNA expression pattern of different molecular subtypes of breast cancer, we proposed that heparinase-1 was co-related with its progression. In addition, genes that were analyzed presented co-expression with heparanase-1. The results that showed that heparanase-1 co-expressed with phosphoinositide 3-kinase adapter protein 1, sialic acid-binding immunoglobulin-like lectin 7, and leukocyte-associated immunoglobulin-like receptor 1 are directed related with immune system evasion during breast cancer progression. Furthermore, cathepsin L was co-expressed with heparanase-1 and transformed inactive heparanase-1 form into active heparanase-1, triggering extracellular matrix remodeling, which contributes to enhanced tumor-host interaction of the tumor.

CONCLUSION

The signaling pathway analysis using bioinformatics tools gives supporting evidence of possible mechanisms related to breast cancer development. Evasion genes of the immune system co-expressed with heparanase-1, a enzyme related with tumor progression.

摘要

目的

研究可能与调节乙酰肝素酶-1机制相关的潜在基因。

方法

分析由圣保罗联邦大学进行,数据来源于:癌症基因组图谱、加利福尼亚大学圣克鲁兹分校基因组浏览器、京都基因与基因组百科全书通路数据库、注释、可视化与整合发现生物信息学数据库以及cBioPortal和Ingenuity Pathway Analysis软件。

结果

利用乳腺癌不同分子亚型的信使核糖核酸表达模式,我们提出乙酰肝素酶-1与其进展相关。此外,所分析的基因与乙酰肝素酶-1呈现共表达。结果表明,与磷脂酰肌醇3-激酶衔接蛋白1、唾液酸结合免疫球蛋白样凝集素7和白细胞相关免疫球蛋白样受体1共表达的乙酰肝素酶-1与乳腺癌进展过程中的免疫逃逸直接相关。此外,组织蛋白酶L与乙酰肝素酶-1共表达,并将无活性的乙酰肝素酶-1形式转化为活性乙酰肝素酶-1,引发细胞外基质重塑,这有助于增强肿瘤与宿主之间的相互作用。

结论

使用生物信息学工具进行的信号通路分析为与乳腺癌发展相关的可能机制提供了支持性证据。与乙酰肝素酶-1共表达的免疫系统逃逸基因,乙酰肝素酶-1是一种与肿瘤进展相关的酶。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c54/7531901/c1c11032c4e4/2317-6385-eins-18-eAO5447-gf01.jpg

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