Evaluation of the effect of TIM-3 suppression by miR-498 and its effect on apoptosis and proliferation rate of HL-60 cell line

Moghaddam Y., Andalib A., Mohammad-Ganji M., Homayouni V., Sharifi M., Ganjalikhani-Hakemi M.

Pathology Research and Practice, vol.214, no.9, pp.1482-1488, 2018 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 214 Issue: 9
  • Publication Date: 2018
  • Doi Number: 10.1016/j.prp.2018.07.019
  • Journal Name: Pathology Research and Practice
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1482-1488
  • Keywords: AML, HL-60, miR-498, miRNA, TIM-3
  • Istanbul Medipol University Affiliated: No


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.