Zhou Jian, Zhang Menghui, Zhang Yan, Shi Xi, Liu Linlin, Yao Ruosi
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, China.
Front Genet. 2021 Sep 10;12:722132. doi: 10.3389/fgene.2021.722132. eCollection 2021.
Multiple myeloma (MM) is a malignant disease of plasma cells, which remains incurable because of its unclear mechanism and drug resistance. Herein, we aimed to explore new biomarkers and therapeutic targets in MM. After screening differentially expressed genes (DEGs) in GSE6477 and GSE13591 dataset, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs using DAVID online database. The results indicated that the downregulated DEGs were mainly enriched in the immune-associated biological process. The protein-protein interaction network was constructed by STRING database, on which we performed module analysis and identified key genes. Gene set enrichment analysis (GSEA) and Kaplan-Meier analysis showed that RRM2 could be a novel biomarker in MM diagnosis. We further confirmed that novel RRM2 inhibitor osalmid inhibited MM cell proliferation and triggered cell cycle S phase arrest. Targeting RRM2 was expected to develop new therapeutic strategies for malignant MM.
多发性骨髓瘤(MM)是一种浆细胞恶性疾病,由于其发病机制不明和耐药性,仍然无法治愈。在此,我们旨在探索MM中的新生物标志物和治疗靶点。在筛选GSE6477和GSE13591数据集中的差异表达基因(DEG)后,我们使用DAVID在线数据库对DEG进行了基因本体论和京都基因与基因组百科全书通路富集分析。结果表明,下调的DEG主要富集在免疫相关生物学过程中。通过STRING数据库构建蛋白质-蛋白质相互作用网络,在此基础上进行模块分析并鉴定关键基因。基因集富集分析(GSEA)和Kaplan-Meier分析表明,RRM2可能是MM诊断中的一种新型生物标志物。我们进一步证实,新型RRM2抑制剂奥沙米特可抑制MM细胞增殖并引发细胞周期S期阻滞。靶向RRM2有望为恶性MM开发新的治疗策略。