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

سال انتشار: 1398
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 339

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شناسه ملی سند علمی:

JR_IJBMS-23-3_014

تاریخ نمایه سازی: 27 مرداد 1399

چکیده مقاله:

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.

کلیدواژه ها:

Bioinformatics ، Biomarker ، miRNA ، Notch signaling pathway ، T-cell acute lymphoblastic leukemia

نویسندگان

Tohid Naderi

Department of laboratory hematology and blood bank, School of allied medicine, Shahid Beheshti University of medical sciences, Tehran, Iran

Samira Mohammadi Yeganeh

Medical nanotechnology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran|Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Neda Mohammadi-Hezaveh

Department of laboratory hematology and blood bank, School of allied medicine, Shahid Beheshti University of medical sciences, Tehran, Iran

Razie Hadavi

Department of Biochemistry, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran|Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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  • Conflict of interest ...
  • The authors confirm that they have no conflicts of interest ...
  • Acknowledgments ...
  • The results described in this paper were part of Tohid ...
  • Wang Z, Li Y, Ahmad A, Azmi AS, Banerjee S, ...
  • Sarmento L, Póvoa V, Nascimento R, Real G, Antunes I, ...
  • Lobry C, Oh P, Mansour MR, Look AT, Aifantis I. ...
  • Hasserjian R, Aster J, Davi F, Weinberg D, Sklar J. ...
  • Liu J, Sato C, Cerletti M, Wagers A. Chapter twelve-notch ...
  • Deftos ML, He Y-W, Ojala EW, Bevan MJ. Correlating notch ...
  • van Limpt V, Chan A, Caron H, Sluis PV, Boon ...
  • Su Q, Xin L. Notch signaling in prostate cancer: refining ...
  • Stylianou S, Clarke RB, Brennan K. Aberrant activation of notch ...
  • Stockhausen MT, Kristoffersen K, Poulsen HS. The functional role of ...
  • Ye Q, Jiang J, Zhan G, Yan W, Huang L, ...
  • Malecki MJ, Sanchez-Irizarry C, Mitchell JL, Histen G, Xu ML, ...
  • Joshi I, Minter LM, Telfer J, Demarest RM, Capobianco AJ, ...
  • Gautschi O, Ratschiller D, Gugger M, Betticher DC, Heighway J. ...
  • Yang CC, Chu KC, Chen HY, Chen WC. Expression of ...
  • Bachmann K, Neumann A, Hinsch A, Nentwich MF, El Gammal ...
  • Cohen B, Shimizu M, Izrailit J, Ng NF, Buchman Y, ...
  • Ghildiyal M, Zamore PD. Small silencing RNAs: an expanding universe. ...
  • Winter J, Jung S, Keller S, Gregory RI, Diederichs S. ...
  • Wang W, Luo Y-p. MicroRNAs in breast cancer: oncogene and ...
  • Abba ML, Patil N, Leupold JH, Moniuszko M, Utikal J, ...
  • Karami F, Mohammadi-Yeganeh S, Abedi N, Koochaki A, Kia V, ...
  • Mohammadi-Yeganeh S, Mansouri A, Paryan M. Targeting of miR9/NOTCH1 interaction ...
  • Mohammadi-Yeganeh S, Paryan M, Samiee SM, Soleimani M, Arefian E, ...
  • Paryan M, Mohammadi-Yeganeh S, Samiee SM, Soleimani M, Arefian E, ...
  • Li X, von Boehmer H. Notch signaling in T-cell development ...
  • Xu Y, Yang J, Li X. MicroRNA-25 promotes T-cell acute ...
  • Shi C, Zhang X, Li X, Zhang L, Li L, ...
  • Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, ...
  • Wang J, Chen J, Sen S. MicroRNA as biomarkers and ...
  • Mavrakis KJ, Van Der Meulen J, Wolfe AL, Liu X, ...
  • Lv M, Zhang X, Jia H, Li D, Zhang B, ...
  • Gusscott S, Kuchenbauer F, Humphries RK, Weng AP. Notch-mediated repression ...
  • Li X, Sanda T, Look AT, Novina CD, von Boehmer ...
  • Mohammadi Yeganeh S, Vasei M, Tavakoli R, Kia V, Paryan ...
  • Weng AP, Millholland JM, Yashiro-Ohtani Y, Arcangeli ML, Lau A, ...
  • Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ, ...
  • Tao J, Zhao X, Tao J. c-MYC–miRNA circuitry: a central ...
  • Christoffersen N, Shalgi R, Frankel L, Leucci E, Lees M, ...
  • Sun F, Fu H, Liu Q, Tie Y, Zhu J, ...
  • Du R, Sun W, Xia L, Zhao A, Yu Y, ...
  • De Weer A, Van der Meulen J, Rondou P, Taghon ...
  • Capuano M, Iaffaldano L, Tinto N, Montanaro D, Capobianco V, ...
  • Shi J, Liu Y, Liu J, Zhou J. Hsa-miR-449a genetic ...
  • Zhang C, Liu J, Tan C, Yue X, Zhao Y, ...
  • Lin N, Zhou Y, Lian X, Tu Y. Expression of ...
  • Jiang L, Li X, Cheng Q, Zhang B-H. Plasma microRNA ...
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