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中国癌症防治杂志

中国癌症防治杂志 ›› 2021, Vol. 13 ›› Issue (2): 170-176.doi: 10.3969/j.issn.1674-5671.2021.02.11

• 基础研究 • 上一篇    下一篇

LncRNA ZEB1⁃AS1对B细胞非霍奇金淋巴瘤增殖和凋亡的影响及其下游调控网络的分析

  

  1. 广西医科大学附属肿瘤医院淋巴血液肿瘤科；广西医科大学生命科学院；广西医科大学第二附属医院药学部；前海人寿广西医院药学部
  • 出版日期:2021-04-25 发布日期:2021-04-30
  • 通讯作者: 卢盛娟 E-mail：424039059@qq.com
  • 基金资助:
    广西自然科学基金项目（2018GXNSFBA281026；2019GXNSFAA245086）；中国博士后科学基金项目（2020M673555XB）

Effect of lncRNA ZEB1?AS1 on the proliferation and apoptosis of B?cell non?Hodgkin's lymphoma and analysis of its downstream regulatory network

  • Online:2021-04-25 Published:2021-04-30

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摘要： 目的 探讨长链非编码 RNA（lncRNA） ZEB1-AS1对B 细胞非霍奇金淋巴瘤（B-cell non-Hodgkin's lymphoma，B-NHL）细胞增殖和凋亡的影响，构建lncRNA、miRNA、mRNA相关竞争性内源RNA（ceRNAs）网络。方法 采用Cox回归模型筛选GEO数据集（GSE31312）中与弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma，DLBCL)预后相关的lncRNAs。采用慢病毒转染技术建立ZEB1-AS1敲低的B-NHL细胞模型，采用CCK-8法和流式细胞术分别检测敲低ZEB1-AS1及不同浓度（50 ng/mL、100 ng/mL、200 ng/mL、400 ng/mL）多柔比星（doxorubicin，Dox）处理后的细胞增殖与凋亡情况。构建以ZEB1-AS1为节点的 lncRNA-miRNA-mRNA ceRNA调控网络，利用GO、KEGG和PPI分析该调控网络下游相关的核心mRNA及其功能。结果 共筛选了20个高风险lncRNAs。预测与ZEB1-AS1有相互结合的miRNA 4个，与ZEB1-AS1呈共表达关系又与miRNA相结合的潜在下游mRNA 1 208个，以此构建lncRNA-miRNA-mRNA调控网络及PPI调控网络。在体外实验中，与空载组相比，敲低ZEB1-AS1可显著抑制细胞增殖和促进细胞凋亡（均P<0.05），敲低ZEB1-AS1+Dox作用对抑制淋巴瘤细胞增殖和促进细胞凋亡有协同作用。结论  ZEB1-AS1敲低可抑制B-NHL细胞增殖和促进细胞凋亡，且可能增强Dox的药物敏感性；以ZEB1-AS1为节点构建的ceRNA调控网络，可能是DLBCL重要的调控机制和诊疗靶点。

关键词: 【关键词】 B细胞非霍奇金淋巴瘤, 弥漫大B细胞淋巴瘤, LncRNA, ZEB1-AS1, 增殖, 凋亡, ceRNA网络

Abstract: Objective  To investigate the effects of long non-coding RNA(lncRNA) ZEB1-AS1 on the proliferation and apoptosis of B-cell non-Hodgkin's lymphoma(B-NHL), and to construct lncRNA, miRNA, mRNA-related competitive endogenous RNA (ceRNAs) network. Methods The Cox regression model was used to screen the lncRNAs related to the prognosis of diffuse large B-cell lymphoma (DLBCL) in the GEO data set (GSE31312). Lentiviral transfection technology was used to establish the ZEB1-AS1 knockdown B-NHL cell model, and the CCK-8 and flow cytometry were used to detect the proliferation and apoptosis of B-NHL cells after treated with ZEB1-AS1 knockdown and different concentrations (50 ng/mL, 100 ng/mL, 200 ng/mL, 400 ng/mL) doxorubicin (Dox). The lncRNA-miRNA-mRNA ceRNA regulatory network was constructed with ZEB1-AS1 as the node, and GO, KEGG and PPI were used to analyze the core mRNA of related to the downstream of the regulatory network and its functions. Results A total of 20 high-risk lncRNAs were screened, and 4 miRNAs binding to ZEB1-AS1 and 1, 208 potential downstream mRNAs co-expressed with ZEB1-AS1 and combined with miRNAs were predicted, so as to construct the lncRNA-miRNA-mRNA regulatory network and the PPI regulatory network.In vitro experiments, knockdown of ZEB1-AS1 could significantly inhibit cell proliferation and promote cell apoptosis compared with the empty group (all P<0.05), and the combination of ZEB1-AS1 knockdown and Dox could synergistically inhibit the cell proliferation and promote the apoptosis. Conclusions ZEB1-AS1 knockdown can inhibit the proliferation and promote the apoptosis of B-NHL cells, enhancing the drug sensitivity of Dox.The ceRNA regulatory network constructed with ZEB1-AS1 as a node may be an important regulatory mechanism and diagnosis and treatment target for DLBCL.

Key words: B-cell non-Hodgkin's lymphoma, Diffuse large B-cell lymphoma, LncRNA, ZEB1-AS1, Proliferation, Apoptosis, ceRNA network

中图分类号: 

  • R733.1