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Evaluation of the Effect of Tim-3 Suppression by Mir-498 and Its Effect on Apoptosis and Proliferation Rate of Hl-60 Cell Line Publisher Pubmed



Moghaddam Y1 ; Andalib A1 ; Mohammadganji M1 ; Homayouni V2 ; Sharifi M3 ; Ganjalikhanihakemi M1, 2
Authors
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Authors Affiliations
  1. 1. Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Acqured Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran

Source: Pathology Research and Practice Published:2018


Abstract

Background: Acute Myeloid Leukemia (AML) is a Cancer of hematopoietic stem cells with a rapid progression. TIM-3 is expressed on leukemic stem cells (LSCs) in most types of AML and might have a positive effect on maintenance of malignant phenotype. MicroRNAs play important roles in either cancer progression or suppression. In this study were evaluated, the inhibitory effect of miR-498 on TIM-3 expression and its impact on proliferation and survival of HL-60 cell line. Methods: Firstly, the probable inhibitory effect of miR-498 on TIM-3 expression was predicted. HL-60 cells were cultured and expression of TIM-3 was induced on the cells using phorbol miristate acetate. The cells were transfected with miR-498 and expression level of TIM-3 were measured using with q-RT-PCR and flow cytometry methods. In addition, the effect of suppression of TIM-3 expression in HL-60 cell line was analyzed with apoptosis and cell proliferation assays. Results: Bioinformatics analyses predicted that miR-498 has high ability to silence TIM-3 gene expression. Our experiments confirmed that miR-498 was able to strongly silence TIM-3 expression (68% silencing) in HL-60 cell line (P < 0.002). Also, the cells with suppressed expression of TIM-3 had a lower proliferation and higher apoptosis rates. Conclusion: Based on our results, the miR-498 can effectively suppress TIM-3 expression in the AML cell line. TIM-3 suppression, in turn, inhibits malignant cell proliferation and induces its apoptosis. Collectively, suppression of TIM-3 by miR-498 can be considered as a potential powerful way for treatment of AML. © 2018 Elsevier GmbH
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