miR145 Suppresses Cell Proliferation by Targeting IGF1R and NRAS Genes in Multiple Myeloma Cells

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.