Involvement Value of FLT-3, c-Myc, STAT3, p27, and HOTAIR Gene Expression in Acute Myeloid Leukemia Patients: A Molecular Perspective to a Novel Leukemogenesis Mechanism.

Naser Shagerdi Esmaeli, Shahin Asadi, Davood Bashash, Sina Salari, Mohsen Hamidpour
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Abstract

Background: The identification of long non-coding RNAs (lncRNAs) in the pathogenesis of acute myeloid leukemia (AML) has marked a new era in the molecular understating of the disease. This study investigated the correlation between the changes in the expression of lncRNAs, including HOTAIR, PVT-1, and CRNDE, and the alteration in the expression profile of FLT-3, c-Myc, STAT3, STAT5, and p27 in AML patients. Materials and Methods: Blood samples were collected from forty-one newly diagnosed AML patients and ten healthy individuals to evaluate the expression levels of the study genes using qRT-PCR analysis. The probable correlation between the gene expressions was determined using Pearson's correlation test. Results: The results showed that while there was a significant elevation in the expression of FLT3, c-Myc, STAT3, and HOTAIR, p27 expression remarkably diminished in AML patients compared to the control group. Also, a correlation was found between the expression of FLT-3 and p27 and the expression of HOTAIR and STAT3. It was assumed that FLT-3 had a role in increasing the proliferative and survival capacity of AML cells, at least partly, through c-Myc-mediated suppression of p27. Moreover, lncRNA HOTAIR showed to be involved in leukemia proliferation assumably by enhancing the expression of STAT3. Conclusion: Overall, the results of gene profile analysis suggested that studying the expression of HOTAIR, FLT-3, c-Myc, STAT3, and p27 could be helpful to AML patients, and each of these genes could be a valuable target for pharmaceutic intervention.

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FLT-3、c-Myc、STAT3、p27和HOTAIR基因表达在急性髓细胞白血病患者中的参与价值:一种新的白血病发生机制的分子视角。
背景:在急性粒细胞白血病(AML)发病机制中鉴定出长非编码RNA(lncRNA)标志着对该疾病的分子理解进入了一个新时代。本研究调查了AML患者中lncRNA(包括HOTIAR、PVT-1和CRNDE)表达的变化与FLT-3、c-Myc、STAT3、STAT5和p27表达谱的变化之间的相关性。材料和方法:从41名新诊断的AML患者和10名健康人的血液样本中收集血液样本,使用qRT-PCR分析来评估研究基因的表达水平。使用Pearson相关检验确定基因表达之间的可能相关性。结果:与对照组相比,AML患者的FLT3、c-Myc、STAT3和HOTIAR的表达显著升高,p27的表达显著降低。此外,发现FLT-3和p27的表达与HOTAIR和STAT3的表达之间存在相关性。据推测,FLT-3至少部分通过c-Myc-介导的p27抑制在增加AML细胞的增殖和存活能力方面发挥作用。此外,lncRNA HOTAIR通过增强STAT3的表达而肯定地参与白血病的增殖。结论:总体而言,基因图谱分析结果表明,研究HOTAIR、FLT-3、c-Myc、STAT3和p27的表达可能有助于AML患者,并且这些基因中的每一个都可能是药物干预的有价值的靶点。
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