SYK identified by bioinformatics analysis promotes the proliferation of multiple myeloma.

IF 2.3 4区医学 Q2 HEMATOLOGY

Expert Review of Hematology Pub Date : 2025-05-20 DOI:10.1080/17474086.2025.2505724

Ju Deng, Peichun Li, Shuo Li, Fengting Liang, Minglin Hong, Ting Zhang, Yanhong Tan, Fanggang Ren, Yaofang Zhang, Zhifang Xu, Hongwei Wang

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引用次数: 0

Abstract

Background: Despite recent advancements, the pathogenesis of multiple myeloma (MM) remains incompletely elucidated, with relapse and therapy resistance persisting as major clinical challenges, underscoring the imperative to identify novel therapeutic targets.

Research design and methods: Differentially expressed genes were initially screened from the GSE6477 and GSE6691 datasets. Subsequent functional annotation and pathway enrichment analyses were conducted utilizing the DAVID bioinformatics platform. A protein-protein interaction network was constructed via the STRING database, followed by module analysis and hub genes identification through CytoHubba plugin. The biological significance of candidate genes was ultimately validated through ex vivo cellular functional assays and in vivo xenograft tumorigenesis experiments in murine models.

Results: Bioinformatics analysis identified spleen tyrosine kinase (SYK) as the most prognostically significant candidate gene (p = 0.027). The SYK-specific inhibitor BAY61-3606 demonstrated time- (p < 0.05) and dose- (p < 0.01) dependent inhibition of MM cell viability, concomitant induction of G2/M phase cell cycle arrest (p < 0.001), and significant promotion of apoptosis (p < 0.05). In vivo experiments utilizing MM xenograft models demonstrated that BAY61-3606 administration significantly attenuated tumor growth kinetics (p < 0.05).

Conclusions: Our findings establish SYK as a therapeutic target in MM, thereby facilitating the development of innovative treatment strategies.

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生物信息学分析发现SYK促进多发性骨髓瘤的增殖。

背景：尽管最近取得了一些进展，但多发性骨髓瘤（MM）的发病机制仍未完全阐明，复发和治疗耐药仍然是主要的临床挑战，强调了寻找新的治疗靶点的必要性。研究设计和方法：首先从GSE6477和GSE6691数据集中筛选差异表达基因。随后利用DAVID生物信息学平台进行功能注释和途径富集分析。通过STRING数据库构建蛋白-蛋白互作网络，通过CytoHubba插件进行模块分析和枢纽基因鉴定。候选基因的生物学意义最终通过体外细胞功能测定和小鼠模型体内异种移植肿瘤发生实验得到验证。结果：生物信息学分析发现脾脏酪氨酸激酶（SYK）是最具预后意义的候选基因（p = 0.027）。SYK特异性抑制剂BAY61-3606显示时间- (p p p p p p p)结论：我们的研究结果确立了SYK作为MM的治疗靶点，从而促进了创新治疗策略的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Hematology HEMATOLOGY-

CiteScore

4.70

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Advanced molecular research techniques have transformed hematology in recent years. With improved understanding of hematologic diseases, we now have the opportunity to research and evaluate new biological therapies, new drugs and drug combinations, new treatment schedules and novel approaches including stem cell transplantation. We can also expect proteomics, molecular genetics and biomarker research to facilitate new diagnostic approaches and the identification of appropriate therapies. Further advances in our knowledge regarding the formation and function of blood cells and blood-forming tissues should ensue, and it will be a major challenge for hematologists to adopt these new paradigms and develop integrated strategies to define the best possible patient care. Expert Review of Hematology (1747-4086) puts these advances in context and explores how they will translate directly into clinical practice.