TY - JOUR ID - 14413 TI - Investigating the inhibitory effect of miR-34a, miR-449a, miR-1827, and miR-106b on target genes including NOTCH1, c-Myc, and CCND1 in human T cell acute lymphoblastic leukemia clinical samples and cell line JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Naderi, Tohid AU - Mohammadi Yeganeh, Samira AU - Mohammadi-Hezaveh, Neda AU - Hadavi, Razie AU - Gharehbaghian, Ahmad AU - Vazifeh Shiran, Nader AU - Fallah Azad, Vahid AU - Paryan, Mahdi AD - Department of laboratory hematology and blood bank, School of allied medicine, Shahid Beheshti University of medical sciences, Tehran, Iran AD - Medical nanotechnology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran AD - Department of Biochemistry, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran AD - Mahak charity hospital, Tehran, Iran AD - Department of Research and Development, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran Y1 - 2020 PY - 2020 VL - 23 IS - 3 SP - 376 EP - 382 KW - Bioinformatics KW - Biomarker KW - miRNA KW - Notch signaling pathway KW - T-cell acute lymphoblastic leukemia DO - 10.22038/ijbms.2019.40695.9615 N2 - Objective(s): microRNAs are small non-coding molecules that regulate gene expression in various biological processes. T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy accompanied with genetic aberrations and accounts for 20% of children’s and adult’s ALL. Notch signaling pathway dysregulation occurs in 60% of T-ALL cases. In the present study, we aimed to determine the relationship between miRNAs and genes involved in Notch signaling pathway. Materials and Methods: Considering the role of the pathway and its down-stream genes in proliferation, differentiation, cell cycle, and apoptosis, NOTCH1, c-Myc, and CCND1 genes were selected as target genes. Using bioinformatics studies, miR-34a, miR-449a, miR-1827, and miR-106b were selected as miRNAs targeting the above-mentioned genes. We evaluated these genes and miRNAs in T-ALL clinical samples as well as Jurkat cell line, in which NOTCH1 is overexpressed. Results: Quantitative Real-Time PCR indicated that NOTCH1, c-Myc, and CCND1 were overexpressed in samples with decreased expression of miR-34a. In addition, we observed that samples with decreased expression of miR-449a showed increased expression of NOTCH1 and CCND1. Furthermore, we analyzed the expression of miR-1827 and miR-106b, which target c-Myc and CCND1, respectively. We found out that the expression of miR-1827, miR-106b, and their respective target genes were inversely correlated in 80% and 75% of the cases (r=0.8), respectively. Furthermore, in Jurkat cell line, the expression of target genes was increased while the candidate miRNAs except miR-34a were decreased. Conclusion: These miRNAs can be proposed as biomarkers and new therapeutic targets in T-ALL patients who have NOTCH1 overexpression. UR - https://ijbms.mums.ac.ir/article_14413.html L1 - https://ijbms.mums.ac.ir/article_14413_d2955d29af2305e90a79e3902646446f.pdf ER -