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基于基因表达谱芯片分析鉴定弥漫性大 B 细胞淋巴瘤相关的潜在关键基因。

Identification of potential key genes associated with diffuse large B-cell lymphoma based on microarray gene expression profiling.

出版信息

Neoplasma. 2017;64(6):824-833. doi: 10.4149/neo_2017_603.

Abstract

The study aimed to screen potential key genes, and their targeted miRNAs and transcription factors (TFs) that were related to diffuse large B-cell lymphoma (DLBCL), and explore potential therapeutic targets for the progression of DLBCL. Dataset GSE56315 extracted from human tonsils was downloaded from Gene Expression Omnibus. Limma package was used to identify differential expression genes (DEG) between DLBCL and normal human tonsils samples, and the function and pathway enrichment analyses were performed. Then, functional interaction (FI) networks analyses of DEGs were implemented, and modules were extracted. Additionally, DLBCL-related miRNAs were predicted based on miR2disease database. Thereafter, TF-target DEGs and miRNAs targeted genes were respectively obtained. Finally, the integrated network of TF-target-miRNA was constructed. A total of 4,495 DEGs were identified between DLBCL and NHT samples. Among them, 114 up-regulated DEGs were contained in 8 modules of FI network, while 189 down-regulated DEGs were contained in 12 sub-modules. In addition, most DEGs were enriched in the function of "DNA binding" and pathways of "chemokine signaling pathway", "phosphatidylinositol signaling system" and "RNA degradation". Moreover, 19 miRNAs related with DLBCL were downloaded from Mirwalk2. Furthermore, miRNAs of miR-21-5p, miR-155 and miR-17-5p, the TF of STAT1, and DEGs such as NUF2, CCR1, PIK3R1, SMC1A, FOXK1 and CNOT6L had high degrees in the integrated networks of TF-target-miRNA. DEGs like NUF2, CCR1, PIK3R1, SMC1A, FOXK1 and CNOT6L might be closely associated with the pathogenesis of DLBCL.

摘要

该研究旨在筛选与弥漫性大 B 细胞淋巴瘤(DLBCL)相关的潜在关键基因及其靶向 microRNA 和转录因子(TFs),并探索 DLBCL 进展的潜在治疗靶点。从基因表达综合数据库中下载了人类扁桃体的数据集 GSE56315。使用 Limma 包来识别 DLBCL 和正常人类扁桃体样本之间的差异表达基因(DEG),并进行功能和通路富集分析。然后,对 DEGs 进行功能相互作用(FI)网络分析,并提取模块。此外,基于 miR2disease 数据库预测与 DLBCL 相关的 microRNA。然后,分别获得 TF 靶标 DEGs 和 microRNA 靶标基因。最后,构建 TF-靶标-miRNA 的综合网络。在 DLBCL 和 NHT 样本之间共鉴定出 4495 个 DEG。其中,FI 网络的 8 个模块中包含 114 个上调的 DEG,12 个亚模块中包含 189 个下调的 DEG。此外,大多数 DEG 富集在“DNA 结合”功能和“趋化因子信号通路”、“磷酸肌醇信号系统”和“RNA 降解”途径中。此外,从 Mirwalk2 下载了 19 个与 DLBCL 相关的 microRNA。此外,miR-21-5p、miR-155 和 miR-17-5p 的 microRNA、STAT1 的 TF 以及 NUF2、CCR1、PIK3R1、SMC1A、FOXK1 和 CNOT6L 等 DEGs 在 TF-靶标-miRNA 的综合网络中具有较高的度数。NUF2、CCR1、PIK3R1、SMC1A、FOXK1 和 CNOT6L 等 DEGs 可能与 DLBCL 的发病机制密切相关。

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