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Mir-192 Overexpression Effect on Dhfr and Tyms in Acute Lymphoblastic Leukemia Publisher



Sayadi M1 ; Rostami S2 ; Nadali F1 ; Fathabad ME3, 4 ; Riazirad F5 ; Sayadi K6 ; Ajdary S5
Authors
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Authors Affiliations
  1. 1. Hematology Department, Allied Medical School, Tehran University of Medical Sciences, Ghods Ave., Tehran, Iran
  2. 2. Hematology and Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Kargar Ave., Tehran, Iran
  3. 3. Department of Laboratory Sciences, Paramedical Faculty, Tabriz University of Medical Sciences, Daneshgah Ave., Tabriz, Iran
  4. 4. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Daneshgah Ave., Tabriz, Iran
  5. 5. Department of Immunology, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran, 13169-43551, Iran
  6. 6. Department of Clinical Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

Source: Gene Reports Published:2020


Abstract

Purpose: Non-coding RNAs play a critical role in gene regulation in cancer cells. Reduced expression of microRNA-192 has been detected in many cancers. Here, we investigated the role of miR-192 in Dihydrofolate reductase (DHFR) and Thymidylate Synthase (TYMS) expression level and in an acute lymphoblastic leukemia cell line. Basic procedures: 20 patients diagnosed with acute lymphoblastic leukemia (ALL) were studied for the level of (micro RNA-192) miR-192, DHFR and TYMS expression level by qRT-PCR. NALM-6 cells were transduced using recombinant lentiviruses for overexpression of miR-192 and its backbone, then the relative changes in DHFR and TYMS genes expression were studied by qRT-PCR. DHFR Protein level changes were analyzed by Western blotting. Main findings: ALL patients with relapse, experience lower levels of miR-192 and higher levels of DHFR and TYMS in comparison with treated patients. Overexpression of miR-192 in NALM-6 cells resulted in decreased expression of DHFR and TYMS. Moreover, the protein level of DHFR was decreased after overexpression of miR-192. Principal conclusions: These results suggest the tumor suppression effects of miR-192 and its correlation with decreased DHFR and TYMS level in acute lymphoblastic leukemia cells for the first time. © 2020