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从进化角度预测七鳃鳗和人类肿瘤的 ATP 酶阳离子转运体 13A2 分子。

Prediction of ATPase cation transporting 13A2 molecule in Petromyzon marinus and pan-cancer analysis into human tumors from an evolutionary perspective.

机构信息

College of Life Sciences, Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China.

出版信息

Immunogenetics. 2021 Aug;73(4):277-289. doi: 10.1007/s00251-021-01216-7. Epub 2021 Mar 20.

Abstract

The ATPase cation transporting 13A2 protein (ATP13A2), which maintains the homeostasis of mitochondria and lysosomes, plays a significant role in human neurodegenerative diseases and cancer. Through constructing a lamprey proteome database, employing multiple sequence alignment and phylogenetic analysis, 5 ATP13A2 proteins from Petromyzon marinus (Pm-ATP13A2) were identified based on the evolutionary perspective. The motif and domain analysis showed that the ATP13A2 protein was conserved. The multiple phosphorylation sites and transmembrane structures highlighted the characteristics of ATP13A2 as the P-ATPase-V cation transporting protein. Based on the information provided by the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, this study was conducted as a preliminary investigation of the carcinogenic effects of the ATP13A2 gene in a variety of tumors. The ATP13A2 was strongly expressed in most tumors, except in two types of nervous system tumors glioblastoma multiforme (GBM) and brain lower grade glioma (LGG). Moreover, the expression of ATP13A2 was strongly correlated with the prognosis of tumor patients. The high expression of ATP13A2 was obviously related to the poor prognosis of LGG. The poor prognosis of LGG patients may affect the ATP13A2 expression through the immune cells and radiotherapy. Also, cancer-related fibroblast infiltration was observed. All in all, this work offers more insights into the molecular evolution of the ATP13A2 protein and facilitates the understanding of the carcinogenic effects of the ATP13A2 in different tumors. Our discussion also promotes the study into the successful evolution of the vertebrate brain and the mechanism of clinical brain-related diseases.

摘要

ATP 酶阳离子转运蛋白 13A2(ATP13A2),它维持着线粒体和溶酶体的内稳态,在人类神经退行性疾病和癌症中起着重要作用。通过构建七鳃鳗蛋白质组数据库,采用多重序列比对和系统发育分析,从 Petromyzon marinus(Pm-ATP13A2)中基于进化的角度鉴定了 5 种 ATP13A2 蛋白。基序和结构域分析表明 ATP13A2 蛋白具有保守性。多个磷酸化位点和跨膜结构突出了 ATP13A2 作为 P-ATPase-V 阳离子转运蛋白的特征。基于癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)提供的信息,本研究初步探讨了 ATP13A2 基因在多种肿瘤中的致癌作用。除两种神经系统肿瘤多形性胶质母细胞瘤(GBM)和脑低级别神经胶质瘤(LGG)外,ATP13A2 在大多数肿瘤中均强烈表达。此外,ATP13A2 的表达与肿瘤患者的预后密切相关。ATP13A2 的高表达与 LGG 的预后不良明显相关。LGG 患者的预后不良可能通过免疫细胞和放疗影响 ATP13A2 的表达。同时,还观察到与癌症相关的成纤维细胞浸润。总之,这项工作为 ATP13A2 蛋白的分子进化提供了更多的见解,并有助于理解 ATP13A2 在不同肿瘤中的致癌作用。我们的讨论也促进了对脊椎动物大脑成功进化和临床相关脑部疾病机制的研究。

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