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研究丝裂原活化蛋白激酶(MAPK)信号通路中的基因(MEK1)在成人T细胞白血病/淋巴瘤(ATLL)诱导中的作用。

Investigating the effect of gene (MEK1) in MAPK pathway in the induction of adult T-cell leukemia/lymphoma (ATLL).

作者信息

Hosseini Parastoo, Rahimi Foroushani Abbas, Marjani Arezoo, Tavakoli Mahnaz, Amiri Abdollah, Hosseini Amin, Bahavar Atefeh, Mozhgani Sayed-Hamidreza, Norouzi Mehdi

机构信息

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Microbiol. 2023 Jun;15(3):475-481. doi: 10.18502/ijm.v15i3.12910.

Abstract

BACKGROUND AND OBJECTIVES

HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the gene. The effects of the gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the gene mutations and the level of gene expression in ATLL patients compared to healthy individuals.

MATERIALS AND METHODS

Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the gene were examined by qRT-PCR, and to check possible mutations in the gene; all samples were sequenced and analyzed by BioEdite Software.

RESULTS

gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database.

CONCLUSION

These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the gene plays a vital role.

摘要

背景与目的

人类嗜T淋巴细胞病毒1型(HTLV-1)可引发两种重要疾病,即热带痉挛性截瘫(HAM/TSP)和成人T细胞白血病/淋巴瘤(ATLL)。全球约有1000万至2000万人感染HTLV-1。识别不同癌症中发生改变的基因对于寻找潜在治疗策略至关重要。RAS/丝裂原活化蛋白激酶(MAPK)信号通路的一种蛋白质是MEK1,它由[具体基因名称]基因产生。该基因对MAPK信号通路的影响尚未完全阐明。本研究旨在确定与健康个体相比,ATLL患者中[具体基因名称]基因突变情况及该基因的表达水平。

材料与方法

本研究纳入了10例ATLL患者和10名健康对照个体。我们使用酶联免疫吸附测定(ELISA)试验筛查抗HTLV-I抗体,并通过聚合酶链反应(PCR)确认感染情况。然后,我们从新鲜全血中提取总RNA,并合成互补DNA(cDNA)。通过实时定量逆转录聚合酶链反应(qRT-PCR)检测[具体基因名称]基因的表达水平,为检测该基因可能存在的突变,对所有样本进行测序并使用BioEdite软件进行分析。

结果

ATLL组中[具体基因名称]基因的表达显著高于健康对照组(P = 0.001)。突变测序分析显示核苷酸212发生了S→R变化,并在不同核苷酸处鉴定到突变,这些突变与通用蛋白质数据库(UniProt)中定义的核苷酸突变完全不同。

结论

这些结果可能为[具体基因名称]基因发挥重要作用的疾病的预防、预后和靶向治疗提供思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c3/10336286/2be38798a67d/IJM-15-475-g001.jpg

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