基于miR-146a/TRAF6轴探讨LncRNA NORAD对非霍奇金淋巴瘤细胞焦亡增殖和侵袭的影响

doi:10.3969/j.issn.1006-6233.2025.07.06

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摘要 目的: 基于微小RNA 146a(miR-146a)和肿瘤坏死因子受体相关蛋白6(TRAF6)探究长链非编码RNA(LncRNA)NORAD对非霍奇金淋巴瘤(NHL)细胞焦亡、增殖和转移的影响。方法: 培养NHL细胞系Jurkat、Raji和正常B细胞,通过实时荧光定量聚合酶链式反应(qRT-PCR)检测LncRNA NORAD、miR-146a和TRAF6表达水平。选择Raji细胞系进行LncRNA NORAD表达敲低处理(NORAD-siNC组,NORAD-si组),通过Western blot检测NOD样受体蛋白3(NLRP3)、Cleaved caspase1、Gasdermins-DN端体(N-GSDMD)、TRAF6表达水平变化,qRT-PCR检测miR-146a表达水平变化,试剂盒检测细胞培养上清中白介素-1β(IL-1β)、IL-18水平变化,EDU实验检测细胞增殖活性变化,Transwell实验检测细胞侵袭活性变化。之后,通过检测双萤光素酶活性验证LncRNA NORAD和miR-146a、miR-146a和TRAF6之间的相关性。结果: 与正常B细胞相比,LncRNA NORAD和TRAF6在Jurkat、Raji细胞中表达升高,miR-146a在Jurkat、Raji细胞中表达降低。与NORAD-siNC组细胞相比,NORAD-si组细胞miR-146a、NLRP3、N-GSDMD、Cleaved caspase1表达水平升高,TRAF6表达水平降低,细胞增殖和侵袭活性减弱,细胞培养上清中IL-1β和IL-18水平均升高。双萤光素酶检测结果表明,LncRNA NORAD和miR-146a、miR-146a和TRAF6之间均存在靶向结合关系。结论: LncRNA NORAD在NHL细胞中表达上调,敲低LncRNA NORAD表达可以通过miR-146a/TRAF6轴诱导NHL细胞焦亡,抑制细胞增殖和侵袭。

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关键词 ：长链非编码RNA NORAD, 非霍奇金淋巴瘤, 细胞焦亡, 微小RNA 146a, 肿瘤坏死因子受体相关蛋白6

Abstract：Objective: To investigate the effect of lncRNA NORAD on pyroptosis, proliferation and invasion of non-Hodgkin's lymphoma cells based on miR-146a/TRAF6 axis. Methods: NHL cell lines Jurkat, Raji and normal B cells were cultured. The expression levels of lncRNA NORAD, miR-146a and TRAF6 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Raji cell line was selected for lncRNA NORAD knockdown treatment (NORAD-siNC group, NORAD-si group). Western blot was used to detect the expression levels of NOD-like receptor protein 3 (NLRP3), Cleaved caspase1, Gasdermins-DN terminal domain (N-GSDMD) and TRAF6. qRT-PCR was used to detect the expression level of miR-146a. The levels of interleukin-1β (IL-1β) and IL-18 in cell culture supernatant were detected by kits. EDU assay was used to detect cell proliferation activity, and Transwell assay was used to detect cell invasion activity. Then, the correlation between lncRNA NORAD and miR-146a, and between miR-146a and TRAF6 was verified by dual-luciferase activity detection. Results: Compared with normal B cells, the expression of lncRNA NORAD and TRAF6 was increased in Jurkat and Raji cells, while the expression of miR-146a was decreased. Compared with cells in the NORAD-siNC group, cells in the NORAD-si group had increased expression levels of miR-146a, NLRP3, N-GSDMD and Cleaved caspase1, decreased expression level of TRAF6, weakened cell proliferation and invasion activities, and increased levels of IL-1β and IL-18 in cell culture supernatant. The results of dual-luciferase assay showed that there were target binding relationships between lncRNA NORAD and miR-146a, and between miR-146a and TRAF6. Conclusion: lncRNA NORAD is up-regulated in NHL cells. Knocking down the expression of lncRNA NORAD can induce pyroptosis of NHL cells and inhibit cell proliferation and invasion through the miR-146a/TRAF6 axis.

Key words： Long non-coding RNA NORAD Non-Hodgkin lymphoma Pyroptosis MicroRNA 146a Tumor necrosis factor receptor-associated protein 6

基金资助:2023年度河北省医学科学研究课题计划,(编号:20230915)

通讯作者: 江莲

引用本文:

李杨, 刁玉巧, 王江娅, 朱秀丽, 江莲. 基于miR-146a/TRAF6轴探讨LncRNA NORAD对非霍奇金淋巴瘤细胞焦亡增殖和侵袭的影响[J]. 河北医学, 2025, 31(7): 1087-1092.
LI Yang, DIAO Yuqiao, et al. Effect of LncRNA NORAD on Pyroptosis Proliferation and Invasion of Non-Hodgkin Lymphoma Cells Based on miR-146a/TRAF6 Axis. HeBei Med, 2025, 31(7): 1087-1092.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.07.06 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I7/1087

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