miR-145-5p suppresses cell proliferation by targeting IGF1R and NRAS genes in multiple myeloma cells
Author:
Kaya Murat1ORCID, Suer Ilknur12ORCID, Ozgur Emre3ORCID, Capik Ozel45ORCID, Karatas Omer Faruk45ORCID, Ozturk Sukru1ORCID, Gezer Ugur3ORCID, Palanduz Sukru1ORCID, Cefle Kivanc1ORCID
Affiliation:
1. Department of Internal Medicine , Division of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University , Istanbul , Türkiye 2. Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University , Istanbul , Türkiye 3. Department of Basic Oncology , Diagnostic Treatment and Care Services, Oncology Institute, Istanbul University , Istanbul , Türkiye 4. Department of Molecular Biology and Genetics , Erzurum Technical University , Erzurum , Türkiye 5. Molecular Cancer Biology Laboratory , High Technology Application and Research Center, Erzurum Technical University , Erzurum , Türkiye
Abstract
Abstract
Objectives
Multiple myeloma (MM) is a common hematological cancer. Hence, it is important to conduct further studies investigating the molecular mechanisms in detail that contributes to myeloma genesis. In addition to genetic changes, epigenetic factors such as miRNAs may influence the expression of myeloma-related genes.
Methods
Our study aimed to detect genes closely related to MM and miRNAs involved in the cancer process by changing the expression of these genes with bioinformatics tools and in vitro methods. Bioinformatics approaches identified hub miRNAs in our study that may have a role in the expression change of genes connected to myeloma. The functional impacts of the chosen miRNA on RPMI8226 and U266 cell lines and the effect of this miRNA on the expression changes of putative target genes were investigated.
Results
The viability of miR-145-5p transfected cells was found to decrease compared to control cells and the expression of IGF1R and NRAS genes were found to be significantly suppressed in both cell lines at mRNA level. Decreased levels of the IGF1R and NRAS genes were confirmed in miR-145-5p transfected cells at the protein level as well as compared to control cells. In addition, IGF1R/miR-145-5p interaction was demonstrated via luciferase reporter assay. However, expression levels of EGFR, KLF4, IRS1, CDK4 and CDK6 candidate genes had no statistically significant difference in miR-145-5p transfected cells compared to control cells.
Conclusions
Mir-145-5p was demonstrated to act as a tumor suppressor miRNA and inhibit the proliferation in MM cell lines via targeting IGF1R and NRAS.
Funder
Istanbul University Scientific Research Projects Coordination
Publisher
Walter de Gruyter GmbH
Subject
Biochemistry (medical),Clinical Biochemistry,Molecular Biology,Biochemistry
Reference32 articles.
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