Comprehensive landscape of the renin-angiotensin system in Pan-cancer: a potential downstream mediated mechanism of SARS-CoV-2.
Comprehensive landscape of the renin-angiotensin system in Pan-cancer: a potential downstream mediated mechanism of SARS-CoV-2.
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泛癌中肾素-血管紧张素系统的综合景观：SARS-CoV-2 的潜在下游介导机制
DOI：
10.7150/ijbs.53312
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发表时间：
2021
影响因子：
9.2
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Cui Y;Chen F;Gao J;Lei M;Wang D;Jin X;Guo Y;Shan L;Chen X
背景资料：SARS-CoV-2是全球COVID-19大流行的原因，它利用与ACE 2（肾素-血管紧张素系统[RAS]的关键组分）结合的机制，随后介导RAS家族的继发性失衡，并导致对宿主的严重损伤。然而，很少有研究揭示SARS-CoV-2对肿瘤作用的机制。方法：从33种癌症类型和超过10，000例样本中提取的人口统计学数据用于确定RAS的综合景观。在组织和细胞系中分析了表达分布、转录前和转录后调节和翻译后修饰（PTM）以及基因组改变、DNA甲基化和m6 A修饰。明确RAS在免疫浸润过程中的临床表型、预后价值和意义。结果如下：与正常组织相比，AGTR 1在肿瘤中的低表达是常见的，而AGTR 2和MAS 1在组织和细胞系中均检测到非常低的表达。卵巢浆液性囊腺癌（OV）和肾透明细胞癌（KIRC）中ACE的差异表达模式与涉及E3连接酶的泛素修饰相关。RAS家族的基因组改变在TCGA泛癌项目中并不常见，与其他成员相比，ACE的改变频率最高。AGTR 1的低表达可能是由启动子的高甲基化引起的。RAS家族的下调与较高的临床分期和较差的生存期（通过疾病特异性生存期[DSS]、总生存期[OS]或无进展间期[PFI]测量）相关，尤其是KIRC中的ACE 2和AGTR 1。ACE-AGTR 1是RAS家族中与免疫浸润相关的经典轴，与大多数癌症中的M2型巨噬细胞、癌症相关成纤维细胞（CAF）和免疫检查点基因呈正相关。结论：ACE、ACE 2、AGT和AGTR 1在33种肿瘤组织中均有不同程度的表达。RAS家族的PTM依赖于泛素化。ACE 2和AGTR 1可能是LGG和KIRC的独立预后因素。SARS-CoV-2可能通过调节RAS家族改变肿瘤微环境，从而影响肿瘤的生物学过程。
Background: SARS-CoV-2, the cause of the worldwide COVID-19 pandemic, utilizes the mechanism of binding to ACE2 (a crucial component of the renin-angiotensin system [RAS]), subsequently mediating a secondary imbalance of the RAS family and leading to severe injury to the host. However, very few studies have been conducted to reveal the mechanism behind the effect of SARS-CoV-2 on tumors. Methods: Demographic data extracted from 33 cancer types and over 10,000 samples were employed to determine the comprehensive landscape of the RAS. Expression distribution, pretranscriptional and posttranscriptional regulation and posttranslational modifications (PTMs) as well as genomic alterations, DNA methylation and m6A modification were analyzed in both tissue and cell lines. The clinical phenotype, prognostic value and significance of the RAS during immune infiltration were identified. Results: Low expression of AGTR1 was common in tumors compared to normal tissues, while very low expression of AGTR2 and MAS1 was detected in both tissues and cell lines. Differential expression patterns of ACE in ovarian serous cystadenocarcinoma (OV) and kidney renal clear cell carcinoma (KIRC) were correlated with ubiquitin modification involving E3 ligases. Genomic alterations of the RAS family were infrequent across TCGA pan-cancer program, and ACE had the highest alteration frequency compared with other members. Low expression of AGTR1 may result from hypermethylation in the promoter. Downregulation of RAS family was linked to higher clinical stage and worse survival (as measured by disease-specific survival [DSS], overall survival [OS] or progression-free interval [PFI]), especially for ACE2 and AGTR1 in KIRC. ACE-AGTR1, a classical axis of the RAS family related to immune infiltration, was positively correlated with M2-type macrophages, cancer-associated fibroblasts (CAFs) and immune checkpoint genes in most cancers. Conclusion: ACE, ACE2, AGT and AGTR1 were differentially expressed in 33 types of cancers. PTM of RAS family was found to rely on ubiquitination. ACE2 and AGTR1 might serve as independent prognostic factors for LGG and KIRC. SARS-CoV-2 might modify the tumor microenvironment by regulating the RAS family, thus affecting the biological processes of cancer.
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DOI：
10.11604/pamj.2019.32.197.15129
发表时间：
2019-01-01
期刊：
The Pan African medical journal
影响因子：
--
作者：
Benenemissi, Ikram Hana;Sifi, Karima;Satta, Dalila
通讯作者：
Satta, Dalila
DOI：
10.3109/10641960903254430
发表时间：
2010-01
期刊：
Clinical and experimental hypertension (New York, N.Y. : 1993)
影响因子：
--
作者：
Kiya Y;Miura S;Fujino M;Imaizumi S;Karnik SS;Saku K
通讯作者：
Saku K
影响因子：
5.7
作者：
Alhakamy NA;Ishiguro S;Uppalapati D;Berkland CJ;Tamura M
通讯作者：
Tamura M
LncRNA2Target v2.0：人类和小鼠lncRNA靶基因的综合数据库
影响因子：
14.9
作者：
Cheng L;Wang P;Tian R;Wang S;Guo Q;Luo M;Zhou W;Liu G;Jiang H;Jiang Q
通讯作者：
Jiang Q
MicroRNA-410 通过靶向胰腺癌中的血管紧张素 II 1 型受体发挥肿瘤抑制剂的作用
影响因子：
4.6
作者：
Guo, Rende;Gu, Jianhua;Gu, Chuan
通讯作者：
Gu, Chuan