多发性骨髓瘤（MM）是继非何杰金淋巴瘤之后第二常见的血液癌症。本研究旨在确定控制组和经普利司通处理的MM细胞株之间差异表达的基因（DEGs）。我们检查了GSE14011微阵列数据集，并使用内置的limma包使用GEO2R统计工具筛选出DEGs。我们使用生物信息学流程来确定差异网络、信号级联和枢纽基因的生存情况。我们实施了两种不同的富集分析，包括ClueGO和Metacore™，以获得最显著DEGs的精确注释。我们基于p值和logFC值从数据集中筛选出了最显著的408个DEGs。使用蛋白质网络分析，我们发现基因UBC、HSP90AB1、HSPH1、HSPA1B、HSPA1L、HSPA6、HSPD1、DNAJB1、HSPE1、DNAJC10、BAG3和DNAJC7具有更高的节点度分布。相反，功能注释表明DEGs主要富集在B细胞受体信号传导、未折叠蛋白质反应、吞噬作用的正调节、HSP70、HSP40依赖性折叠和泛素-蛋白酶体分解等方面。使用网络算法并比较富集分析，我们发现富集的枢纽基因是INHBE、UBC、HSPA1A、HSP90AB1、IKBKB和BAG3。这些DEGs进一步通过总生存和肿瘤和对照组基因表达分析验证。最后，在IM9和U266 MM细胞组成的细胞系模型中独立验证了普利司通的效果。普利司通以剂量依赖方式诱导MM细胞的体外细胞毒性。普利司通通过验证生物信息学发现，抑制NF-κB、诱导泛素化蛋白的积累和抑制HSP60，而普利司通诱导的caspase-3和PARP剪切确认了细胞死亡。综上所述，我们发现，由于普利司通处理导致的MM细胞株中诱导的凋亡与识别的DEGs密切相关，并且来自普利司通的联合治疗可以作为新型抗骨髓瘤多功能药物。版权所有©2023 Elsevier Inc.

Multiple myeloma (MM) is the 2nd most frequently diagnosed blood cancer after non-Hodgkin's lymphoma. The present study aimed to identify the differentially expressed genes (DEGs) between the control and pristimerin-treated MM cell lines. We examined the GSE14011 microarray dataset and screened DEGs with GEO2R statistical tool using the inbuilt limma package. We used a bioinformatics pipeline to identify the differential networks, signaling cascades, and the survival of the hub genes. We implemented two different enrichment analysis including ClueGO and Metacore™, to get accurate annotation for most significant DEGs. We screened the most significant 408 DEGs from the dataset based on p-values and logFC values. Using protein network analysis, we found the genes UBC, HSP90AB1, HSPH1, HSPA1B, HSPA1L, HSPA6, HSPD1, DNAJB1, HSPE1, DNAJC10, BAG3, and DNAJC7 had higher node degree distribution. In contrast, the functional annotation provided that the DEGs were predominantly enriched in B-cell receptor signaling, unfolded protein response, positive regulation of phagocytosis, HSP70, and HSP40-dependent folding, and ubiquitin-proteasomal proteolysis. Using network algorithms, and comparing enrichment analysis, we found the hub genes enriched were INHBE, UBC, HSPA1A, HSP90AB1, IKBKB, and BAG3. These DEGs were further validated with overall survival and gene expression analysis between the tumor and control groups. Finally, pristimerin effects were validated independently in a cell line model consisting of IM9 and U266 MM cells. Pristimerin induced in vitro cytotoxicity in MM cells in a dose-dependent manner. Pristimerin inhibited NF-κB, induced accumulation of ubiquitinated proteins and inhibited HSP60 in the validation of bioinformatics findings, while pristimerin-induced caspase-3 and PARP cleavage confirmed cell death. Taken together, we found that the identified DEGs were strongly associated with the apoptosis induced in MM cell lines due to pristimerin treatment, and combinatorial therapy derived from pristimerin could act as novel anti-myeloma multifunctional agents.Copyright © 2023. Published by Elsevier Inc.