Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo

Background: The acidic extracellular environment of tumors has been shown to affect the malignant progression of tumor cells by modulating proliferation, cell death or metastatic potential. The aim of the study was to analyze whether acidosis-dependent miRNAs play a role in the signaling cascade fro...

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Autores principales:	Mandy Rauschner, Thea Hüsing, Luisa Lange, Kristin Jarosik, Sarah Reime, Anne Riemann, Oliver Thews
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Acidosis microRNA Gene expression Migration Proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1c3ccacfdc1144ccb19cd56e2d4a8f81
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spelling	oai:doaj.org-article:1c3ccacfdc1144ccb19cd56e2d4a8f812021-11-30T04:14:40ZRole of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo1476-558610.1016/j.neo.2021.11.005https://doaj.org/article/1c3ccacfdc1144ccb19cd56e2d4a8f812021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1476558621000956https://doaj.org/toc/1476-5586Background: The acidic extracellular environment of tumors has been shown to affect the malignant progression of tumor cells by modulating proliferation, cell death or metastatic potential. The aim of the study was to analyze whether acidosis-dependent miRNAs play a role in the signaling cascade from low pH through changes in gene expression to functional properties of tumors in vitro and in vivo.Methods: In two experimental tumor lines the expression of 13 genes was tested under acidic conditions in combination with overexpression or downregulation of 4 pH-sensitive miRNAs (miR-7, 183, 203, 215). Additionally, the impact on proliferation, cell cycle distribution, apoptosis, necrosis, migration and cell adhesion were measured.Results: Most of the genes showed a pH-dependent expression, but only a few of them were additionally regulated by miRNAs in vitro (Brip1, Clspn, Rif1) or in vivo (Fstl, Tlr5, Txnip). Especially miR-215 overexpression was able to counteract the acidosis effect in some genes. The impact on proliferation was cell line-dependent and most pronounced with overexpression of miR-183 and miR-203, whereas apoptosis and necrosis were pH-dependent but not influenced by miRNAs. The tumor growth was markedly regulated by miR-183 and miR-7. In addition, acidosis had a strong effect on cell adhesion, which could be modulated by miR-7, miR-203 and miR-215.Conclusions: The results indicate that the acidosis effect on gene expression and functional properties of tumor cells could be mediated by pH-dependent miRNAs. Many effects were cell line dependent and therefore do not reflect universal intracellular signaling cascades. However, the role of miRNAs in the adaptation to an acidic environment may open new therapeutic strategies.Mandy RauschnerThea HüsingLuisa LangeKristin JarosikSarah ReimeAnne RiemannOliver ThewsElsevierarticleAcidosismicroRNAGene expressionMigrationProliferationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENNeoplasia: An International Journal for Oncology Research, Vol 23, Iss 12, Pp 1275-1288 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acidosis microRNA Gene expression Migration Proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Acidosis microRNA Gene expression Migration Proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mandy Rauschner Thea Hüsing Luisa Lange Kristin Jarosik Sarah Reime Anne Riemann Oliver Thews Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo
description	Background: The acidic extracellular environment of tumors has been shown to affect the malignant progression of tumor cells by modulating proliferation, cell death or metastatic potential. The aim of the study was to analyze whether acidosis-dependent miRNAs play a role in the signaling cascade from low pH through changes in gene expression to functional properties of tumors in vitro and in vivo.Methods: In two experimental tumor lines the expression of 13 genes was tested under acidic conditions in combination with overexpression or downregulation of 4 pH-sensitive miRNAs (miR-7, 183, 203, 215). Additionally, the impact on proliferation, cell cycle distribution, apoptosis, necrosis, migration and cell adhesion were measured.Results: Most of the genes showed a pH-dependent expression, but only a few of them were additionally regulated by miRNAs in vitro (Brip1, Clspn, Rif1) or in vivo (Fstl, Tlr5, Txnip). Especially miR-215 overexpression was able to counteract the acidosis effect in some genes. The impact on proliferation was cell line-dependent and most pronounced with overexpression of miR-183 and miR-203, whereas apoptosis and necrosis were pH-dependent but not influenced by miRNAs. The tumor growth was markedly regulated by miR-183 and miR-7. In addition, acidosis had a strong effect on cell adhesion, which could be modulated by miR-7, miR-203 and miR-215.Conclusions: The results indicate that the acidosis effect on gene expression and functional properties of tumor cells could be mediated by pH-dependent miRNAs. Many effects were cell line dependent and therefore do not reflect universal intracellular signaling cascades. However, the role of miRNAs in the adaptation to an acidic environment may open new therapeutic strategies.
format	article
author	Mandy Rauschner Thea Hüsing Luisa Lange Kristin Jarosik Sarah Reime Anne Riemann Oliver Thews
author_facet	Mandy Rauschner Thea Hüsing Luisa Lange Kristin Jarosik Sarah Reime Anne Riemann Oliver Thews
author_sort	Mandy Rauschner
title	Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo
title_short	Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo
title_full	Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo
title_fullStr	Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo
title_full_unstemmed	Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo
title_sort	role of acidosis-sensitive micrornas in gene expression and functional parameters of tumors in vitro and in vivo
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/1c3ccacfdc1144ccb19cd56e2d4a8f81
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Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo

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