Analysis of the Main Checkpoints of the JNK-MAPK Pathway in HTLV-1-Associated Leukemia/Lymphoma via Boolean Network Simulation.

IF 2.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical Genetics Pub Date : 2024-09-25 DOI:10.1007/s10528-024-10916-0

Shayan Mardi, Arash Letafati, Amin Hosseini, Reza Faraji, Parastoo Hosseini, Sayed-Hamidreza Mozhgani

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引用次数: 0

Abstract

The c-Jun N-terminal kinase (JNK) pathway is a signal transduction pathway that plays a critical role in cell growth and survival. Its dysregulation is related to various cancers, including adult T-cell leukemia/lymphoma (ATLL), an aggressive peripheral T-cell malignancy caused by human T-cell lymphotropic virus type 1 (HTLV-1) infection. There is currently no vaccine or definitive treatment for ATLL. This research aimed to identify the JNK-MAPK pathway checkpoints to identify possible therapeutic targets using Boolean network analysis. First, the genes involved in the JNK pathway and their interactions were identified and mapped. Next, a Boolean network analysis was performed using the R programming language, which suggested protein kinase B (AKT) and MAP kinase phosphatase (MKP) for further evaluation. Finally, to confirm the effect of these two genes, a clinical study was conducted among ATLL patients and healthy individuals. The quantitative real time polymerase chain reaction (qRT‒PCR) results revealed a statistically significant decrease in the expression of AKT and MKP in ATLL patients compared to normal controls. This highlights the potential role of these two genes as potential therapeutic targets in ATLL.

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通过布尔网络模拟分析 HTLV-1 相关白血病/淋巴瘤中 JNK-MAPK 通路的主要检查点

c-Jun N-末端激酶（JNK）通路是一种信号转导通路，在细胞生长和存活过程中起着至关重要的作用。它的失调与多种癌症有关，包括成人 T 细胞白血病/淋巴瘤（ATLL），这是一种由人类 T 细胞淋巴细胞病毒 1 型（HTLV-1）感染引起的侵袭性外周 T 细胞恶性肿瘤。目前还没有针对 ATLL 的疫苗或确切治疗方法。这项研究旨在通过布尔网络分析确定JNK-MAPK通路检查点，从而确定可能的治疗靶点。首先，确定并绘制了参与 JNK 通路及其相互作用的基因。接着，使用 R 编程语言进行了布尔网络分析，提出了进一步评估的蛋白激酶 B（AKT）和 MAP 激酶磷酸酶（MKP）。最后，为了证实这两个基因的作用，对 ATLL 患者和健康人进行了临床研究。定量实时聚合酶链反应（qRT-PCR）结果显示，与正常对照组相比，ATLL 患者体内 AKT 和 MKP 的表达明显减少。这突显了这两个基因作为 ATLL 潜在治疗靶点的潜在作用。

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来源期刊

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.