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:: Volume 14, Issue 3 (Atumn 2017) ::
Sci J Iran Blood Transfus Organ 2017, 14(3): 217-226 Back to browse issues page
The Effects of Msi2 Knock down on Expression Levels of Musashi2-Numb Pathway and Genes Involved in the Proliferation and Apoptosis of Chronic Myeloid Leukemia Cells
F. Moradi , S. Babashah , M. Sadeghizadeh
Keywords: Key words: Leukemia, Chronic Myeloid, Cell Proliferation, Apoptosis
Full-Text [PDF 602 kb]   (1332 Downloads)     |   Abstract (HTML)  (4757 Views)
Type of Study: Research | Subject: Hematology and Oncology
Published: 2017/09/11
Full-Text:   (1594 Views)
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Sci J Iran Blood Transfus Organ 2017; 13(4): 217-226
Original Article
 

 

The Effects of Msi2 Knock down on Expression Levels
 of Musashi2-Numb Pathway and Genes Involved in the  Proliferation and Apoptosis of Chronic Myeloid
Leukemia Cells
 
Moradi F.1, Babashah S.1, Sadeghizadeh M.1
 
 
1Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
 
Abstract
Background and Objectives
The expression of Numb as a cell-fate determinant gene leads to inhibition of leukemic cell growth. The high levels of Musashi2 (Msi2) results in down-regulation of Numb in chronic myeloid leukemia cells. In this study we knocked down Msi2 using RNA interference (RNAi) strategy and investigated the effects of this knock down on the expression of Musashi2-Numb axis and genes involved in proliferation and apoptosis.
 
Materials and Methods
In this experimental study, synthetic double stranded siRNAs designed to target human Msi2 were transfected to K562 cells using Lipofectamine in duplicate. Changes in the expression levels of Msi-2, Numb, P21, and Bcl-2 genes 48h after transfection were evaluated by real-time PCR. Induction of apoptosis in transfected leukemic cells was determined using Annexin-PI staining and flowcytometry analysis. Data were analyzed by t-test.
 
Results
We found that upon Msi2 suppression, the expression levels of the cell-fate determinant Numb showed two-fold increase in K562 cells (p < 0/05). Msi2 down-regulation and subsequent increase in Numb expression levels caused the elevated expression of p21, as a cell cycle regulator (p < 0/05). In addition, Msi2 down-regulation promoted cell apoptosis via the down-regulation of Bcl-2 expression (p < 0/05). We observed that the rates of apoptosis in leukemic increased to 52% and 60%, 24h and 48h after transfection.
 
Conclusions 
It seems that Msi2 could be an option for targeting leukemic cells and its down-regulation through RNAi strategy may lead to induction of apoptosis in leukemic cells. This approach may open up new opportunities for leukemia therapy.
 
Key words: Leukemia، Chronic Myeloid, Cell Proliferation, Apoptosis
 
 
 
 
 
 
Received:    5 Feb 2017
Accepted: 20 May 2017
 
 

Correspondence: Babashah S., PhD of Molecular Genetics. Assistant Professor of Faculty of Biological Sciences, Tarbiat Modares University.
Postal Code: 1411713116, Tehran, Iran. Tel: (+9821) 82884468; Fax: (+9821) 82884717
E-mail:
 sadegh.babashah@gmail.com
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Moradi F, Babashah S, Sadeghizadeh M. The Effects of Msi2 Knock down on Expression Levels of Musashi2-Numb Pathway and Genes Involved in the Proliferation and Apoptosis of Chronic Myeloid Leukemia Cells. Sci J Iran Blood Transfus Organ 2017; 14 (3) :217-226
URL: http://bloodjournal.ir/article-1-1108-en.html
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Volume 14, Issue 3 (Atumn 2017) Back to browse issues page
فصلنامه پژوهشی خون Scientific Journal of Iran Blood Transfus Organ
The Scientific Journal of Iranian Blood Transfusion Organization - Copyright 2006 by IBTO
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