Department of Hematology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu 214200, P.R. China.
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Mol Med Rep. 2018 Jun;17(6):8129-8136. doi: 10.3892/mmr.2018.8911. Epub 2018 Apr 20.
Nuclear factor‑κB (NF‑κB) is widely involved in various lymphoid malignancies. However, its exact functional role and potential regulatory mechanisms in Hodgkin's lymphoma (HL) remains unclear. The present study aimed to investigate the regulatory mechanism of NF‑κB in HL by analysis of a gene expression profile that was obtained from HL cells with or without NF‑κB subunit 2 (NFKB2) knockdown. The GSE64234 dataset containing 6 HL cell line specimens transfected with small interfering (si)RNA against NFKB2 and 6 control specimens transfected with non‑targeting siRNA sequences was downloaded from the Gene Expression Omnibus database. Based on these data, differentially expressed genes (DEGs) were screened for following data preprocessing. Functional enrichment analysis was subsequently conducted among the identified upregulated and downregulated DEGs. Additionally, a protein‑protein interaction (PPI) network was constructed and module analyses were performed. Finally, microRNAs (miRNAs/miRs) targeting the identified DEGs were predicted for the construction of a miRNA‑target regulatory network. A total of 253 DEGs were identified, consisting of 109 upregulated and 144 downregulated DEGs. Pathway enrichment analysis revealed that B‑cell lymphoma 2‑like 1 (BCL2L1) was significantly enriched in the NF‑κB signaling pathway, and colony‑stimulating factor 2 (CSF2) and BCL2L1 were enriched in the Jak‑signal transducer and activator of transcription (STAT) signaling pathway. BCL2L1 and CSF2 were determined to be hub genes in the PPI network. A total of 6 miRNAs, including let‑7a‑5p, miR‑9‑5p, miR‑155‑5p, miR‑135a‑5p, miR‑17‑5p and miR‑375, were identified in the miRNA‑target regulatory network. The results of the present study indicated that NFKB2 may be involved in HL development through regulation of BCL2L1, CSF2, miR‑135a‑5p, miR‑155‑5p and miR‑9‑5p expression, as well as the modulation of Jak‑STAT and NF‑κB signaling pathways.
核因子-κB（NF-κB）广泛参与各种淋巴恶性肿瘤。然而，其在霍奇金淋巴瘤（HL）中的确切功能作用和潜在调控机制尚不清楚。本研究旨在通过分析 NF-κB 亚基 2（NFKB2）敲低的 HL 细胞的基因表达谱，研究 NF-κB 在 HL 中的调控机制。从基因表达综合数据库中下载了包含 6 个 HL 细胞系标本的 GSE64234 数据集，这些标本经 NFKB2 小干扰（si）RNA 转染，6 个对照标本经非靶向 siRNA 序列转染。基于这些数据，在进行数据预处理后筛选差异表达基因（DEG）。随后对鉴定出的上调和下调 DEG 进行功能富集分析。此外，构建蛋白-蛋白相互作用（PPI）网络并进行模块分析。最后，预测针对鉴定出的 DEG 的 microRNA（miRNA/miRs），构建 miRNA-靶调控网络。共鉴定出 253 个 DEG，包括 109 个上调 DEG 和 144 个下调 DEG。通路富集分析显示，B 细胞淋巴瘤 2 样 1（BCL2L1）在 NF-κB 信号通路中显著富集，集落刺激因子 2（CSF2）和 BCL2L1 在 Jak-信号转导和转录激活因子（STAT）信号通路中富集。BCL2L1 和 CSF2 被确定为 PPI 网络中的枢纽基因。在 miRNA-靶调控网络中共鉴定出 6 个 miRNA，包括 let-7a-5p、miR-9-5p、miR-155-5p、miR-135a-5p、miR-17-5p 和 miR-375。本研究结果表明，NFKB2 可能通过调节 BCL2L1、CSF2、miR-135a-5p、miR-155-5p 和 miR-9-5p 的表达，以及调节 Jak-STAT 和 NF-κB 信号通路，参与 HL 的发生发展。
