Danial Mehranfard, Gabriela Perez, Andres Rodriguez, Julia M Ladna, Christopher T Neagra, Benjamin Goldstein, Timothy Carroll, Alice Tran, Malav Trivedi, Robert C Speth
{"title":"结直肠癌中肾素-血管紧张素系统成分及相关蛋白基因表达的改变","authors":"Danial Mehranfard, Gabriela Perez, Andres Rodriguez, Julia M Ladna, Christopher T Neagra, Benjamin Goldstein, Timothy Carroll, Alice Tran, Malav Trivedi, Robert C Speth","doi":"10.1155/2021/9987115","DOIUrl":null,"url":null,"abstract":"<p><strong>Materials and methods: </strong>Quantitative expression of the RNA of these 17 genes in normal and cancerous tissues obtained using chip arrays from the public functional genomics data repository, Gene Expression Omnibus (GEO) application, was compared statistically.</p><p><strong>Results: </strong>Expression of four genes, <i>AGT</i> (angiotensinogen), <i>ENPEP</i> (aminopeptidase A) <i>MME</i> (neprilysin), and <i>PREP</i> (prolyl endopeptidase), was significantly upregulated in CRC specimens. Expression of <i>REN</i> (renin), <i>THOP</i> (thimet oligopeptidase), <i>NLN</i> (neurolysin), <i>PRCP</i> (prolyl carboxypeptidase), <i>ANPEP</i> (aminopeptidase N), and <i>MAS1</i> (Mas receptor) was downregulated in CRC specimens.</p><p><strong>Conclusions: </strong>Presuming gene expression parallel protein expression, these results suggest that increased production of the angiotensinogen precursor of angiotensin (ANG) peptides, with the reduction of the enzymes that metabolize it to ANG II, can lead to accumulation of angiotensinogen in CRC tissues. Downregulation of <i>THOP</i>, <i>NLN</i>, <i>PRCP</i>, and <i>MAS1</i> gene expression, whose proteins contribute to the ACE2/ANG 1-7/Mas axis, suggests that reduced activity of this RAS branch could be permissive for oncogenicity. Components of the RAS may be potential therapeutic targets for treatment of CRC.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2021-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277508/pdf/","citationCount":"0","resultStr":"{\"title\":\"Alterations in Gene Expression of Renin-Angiotensin System Components and Related Proteins in Colorectal Cancer.\",\"authors\":\"Danial Mehranfard, Gabriela Perez, Andres Rodriguez, Julia M Ladna, Christopher T Neagra, Benjamin Goldstein, Timothy Carroll, Alice Tran, Malav Trivedi, Robert C Speth\",\"doi\":\"10.1155/2021/9987115\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Materials and methods: </strong>Quantitative expression of the RNA of these 17 genes in normal and cancerous tissues obtained using chip arrays from the public functional genomics data repository, Gene Expression Omnibus (GEO) application, was compared statistically.</p><p><strong>Results: </strong>Expression of four genes, <i>AGT</i> (angiotensinogen), <i>ENPEP</i> (aminopeptidase A) <i>MME</i> (neprilysin), and <i>PREP</i> (prolyl endopeptidase), was significantly upregulated in CRC specimens. Expression of <i>REN</i> (renin), <i>THOP</i> (thimet oligopeptidase), <i>NLN</i> (neurolysin), <i>PRCP</i> (prolyl carboxypeptidase), <i>ANPEP</i> (aminopeptidase N), and <i>MAS1</i> (Mas receptor) was downregulated in CRC specimens.</p><p><strong>Conclusions: </strong>Presuming gene expression parallel protein expression, these results suggest that increased production of the angiotensinogen precursor of angiotensin (ANG) peptides, with the reduction of the enzymes that metabolize it to ANG II, can lead to accumulation of angiotensinogen in CRC tissues. Downregulation of <i>THOP</i>, <i>NLN</i>, <i>PRCP</i>, and <i>MAS1</i> gene expression, whose proteins contribute to the ACE2/ANG 1-7/Mas axis, suggests that reduced activity of this RAS branch could be permissive for oncogenicity. Components of the RAS may be potential therapeutic targets for treatment of CRC.</p>\",\"PeriodicalId\":17330,\"journal\":{\"name\":\"Journal of the Renin-Angiotensin-Aldosterone System\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2021-07-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277508/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the Renin-Angiotensin-Aldosterone System\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1155/2021/9987115\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Renin-Angiotensin-Aldosterone System","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2021/9987115","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
引用次数: 0
摘要
材料与方法:使用来自公共功能基因组学数据储存库--基因表达总库(GEO)应用程序的芯片阵列,对正常组织和癌症组织中这17个基因的RNA定量表达进行统计比较:结果:AGT(血管紧张素原)、ENPEP(氨肽酶 A)、MME(肾蛋白酶)和 PREP(脯氨酰内肽酶)这四个基因的表达在 CRC 标本中显著上调。REN(肾素)、THOP(thimet低聚肽酶)、NLN(神经溶解素)、PRCP(脯氨酰羧肽酶)、ANPEP(氨肽酶N)和MAS1(Mas受体)在CRC标本中的表达下调:结论:假设基因表达与蛋白表达平行,这些结果表明,血管紧张素(ANG)肽前体血管紧张素原的生成增加,而将其代谢为 ANG II 的酶减少,可导致血管紧张素原在 CRC 组织中蓄积。THOP、NLN、PRCP 和 MAS1 基因表达的下调(其蛋白有助于 ACE2/ANG 1-7/Mas 轴)表明,RAS 分支的活性降低可能会导致致癌。RAS 的组成成分可能是治疗 CRC 的潜在治疗靶点。
Alterations in Gene Expression of Renin-Angiotensin System Components and Related Proteins in Colorectal Cancer.
Materials and methods: Quantitative expression of the RNA of these 17 genes in normal and cancerous tissues obtained using chip arrays from the public functional genomics data repository, Gene Expression Omnibus (GEO) application, was compared statistically.
Results: Expression of four genes, AGT (angiotensinogen), ENPEP (aminopeptidase A) MME (neprilysin), and PREP (prolyl endopeptidase), was significantly upregulated in CRC specimens. Expression of REN (renin), THOP (thimet oligopeptidase), NLN (neurolysin), PRCP (prolyl carboxypeptidase), ANPEP (aminopeptidase N), and MAS1 (Mas receptor) was downregulated in CRC specimens.
Conclusions: Presuming gene expression parallel protein expression, these results suggest that increased production of the angiotensinogen precursor of angiotensin (ANG) peptides, with the reduction of the enzymes that metabolize it to ANG II, can lead to accumulation of angiotensinogen in CRC tissues. Downregulation of THOP, NLN, PRCP, and MAS1 gene expression, whose proteins contribute to the ACE2/ANG 1-7/Mas axis, suggests that reduced activity of this RAS branch could be permissive for oncogenicity. Components of the RAS may be potential therapeutic targets for treatment of CRC.
期刊介绍:
JRAAS is a peer-reviewed, open access journal, serving as a resource for biomedical professionals, primarily with an active interest in the renin-angiotensin-aldosterone system in humans and other mammals. It publishes original research and reviews on the normal and abnormal function of this system and its pharmacology and therapeutics, mostly in a cardiovascular context but including research in all areas where this system is present, including the brain, lungs and gastro-intestinal tract.