Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo
| Autor: | Luisa Lange, S Reime, Thea Hüsing, Oliver Thews, Anne Riemann, Kristin Jarosik, Mandy Rauschner |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research Programmed cell death Per3 period circadian clock 3 Rif1 replication timing regulatory factor 1 Cell Proliferation Fstl1 follistatin like 1 Gls2 glutaminase 2 microRNA Gene expression miRNA microRNA medicine Animals Rats Wistar Cell adhesion Ikbke inhibitor of kappa light polypeptide gene enhancer in B-cells kinase epsilon RC254-282 Migration Tlr5 toll-like receptor 5 Original Research Txnip thioredoxin interacting protein Crem cAMP responsive element modulator Chemistry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Il6r interleukin 6 receptor Neoplasms Experimental Cell cycle Cell biology Rats Gene Expression Regulation Neoplastic Dnajc25 DnaJ heat shock protein family (Hsp40) member C25 MicroRNAs medicine.anatomical_structure Ercc6l ERCC excision repair 6 like spindle assembly checkpoint helicase MIBG meta-iodobenzylguanidine Acidosis Intracellular TXNIP Brip1 BRCA1 interacting protein C-terminal helicase 1 Clspn claspin |
| Zdroj: | Neoplasia (New York, N.Y.) Neoplasia: An International Journal for Oncology Research, Vol 23, Iss 12, Pp 1275-1288 (2021) |
| ISSN: | 1476-5586 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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