基础医学与临床 ›› 2023, Vol. 43 ›› Issue (7): 1060-1068.doi: 10.16352/j.issn.1001-6325.2023.07.1060

• 研究论文 • 上一篇    下一篇

STAT1诱导的LINC00987调节miR-223-3p/FZD4促进人胶质母细胞瘤相关巨噬细胞向M2型极化

张宝瑞1, 马春晓2, 秦历杰1,*   

  1. 1.河南省人民医院 急诊科,河南 郑州 450003;
    2.河南省人民医院 神经外科,河南 郑州 450003
  • 收稿日期:2022-05-20 修回日期:2022-11-22 出版日期:2023-07-05 发布日期:2023-07-05
  • 通讯作者: *qlj171819@163.com
  • 基金资助:
    河南省医学科技攻关计划省部共建项目(SB201901082)

STAT1-induced LINC00987 regulates miR-223-3p/FZD4 and promotes M2-type polarization of human glioblastoma-associated macrophages

ZHANG Baorui1, MA Chunxiao2, QIN Lijie1,*   

  1. 1. Department of Emergency, Henan Provincial People’s Hospital, Zhengzhou 450003, China;
    2. Department of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China;
  • Received:2022-05-20 Revised:2022-11-22 Online:2023-07-05 Published:2023-07-05

摘要: 目的 本研究旨在探讨STAT1激活的LINC00987对人胶质母细胞瘤(GBM)相关巨噬细胞向M2型极化的影响。方法 通过GEO数据库分析筛选出GBM中表达失调的lncRNAs。RT-qPCR检测LINC00987、miR-223-3p、卷曲蛋白4基因(FZD4)的表达。将人单核细胞白血病细胞系THP-1分别诱导成M0、M1、M2型巨噬细胞,并将GBM细胞与THP-1细胞共培养,流式细胞测量术检测CD14+/CD206+巨噬细胞的占比,ELISA检测M2型巨噬细胞相关因子(VEGF、TGF-β1)的表达。结果 相对于癌旁组织和人正常神经胶质细胞系HEB,GBM组织和细胞中的LINC00987、FZD4表达上调而miR-223-3p表达下调(P<0.05)。在GBM细胞中,STAT1能够激活LINC00987并影响miR-223-3p/FZD4轴。过表达LINC00987能够促进GBM相关巨噬细胞向M2型极化(P<0.05)。敲减LINC00987则能够抑制GBM相关巨噬细胞向M2型极化,但该作用能被miR-223-3p抑制剂部分挽救(P<0.05)。敲减FZD4能够抑制GBM相关巨噬细胞向M2型极化,但该作用能被过表达LINC00987部分挽救(P<0.05)。结论 STAT1激活的LINC00987调节miR-223-3p/FZD4轴诱导GBM相关巨噬细胞向M2型极化。

关键词: 胶质母细胞瘤, LINC00987, miR-223-3p, M2型巨噬细胞极化

Abstract: Objective To investigate the effects of LINC00987 activated by STAT1 on M2-type polarization of human glioblastoma (GBM) associated macrophages. Methods LncRNAs with dysregulated expression in GBM were screened by GEO analysis. The expression of LINC00987, miR-223-3p and FZD4 was detected by RT-qPCR. THP-1 cells were induced into M0, M1, and M2 macrophages, and GBM cells were co-cultured with THP-1 cells. The proportion of CD14+/CD206+ macrophages was detected by flow cytometry, The expression of M2-type macrophage-related factors (VEGF, TGF-β1) was detected by ELISA. Over-expression of LINC00987 promoted the M2-type polarization of GBM-related macrophages (P<0.05). FZD4 knockdown inhibited M2-type polarization of GBM-related macrophages, but this effect was partially reversed by over expression of LINC00987(P<0.05). Results Compared with paracancerous tissues and HEB cells, the expressions of LINC00987 and FZD4 in GBM tissues and cells were up-regulated while the expression of miR-223-3p was down-regulated(P<0.05). In GBM cells, STAT1 activated LINC00987 and affected miR-223-3p/FZD4 axis. LINC00987 knockdown inhibited M2-type polarization of GBM-related macrophages, but this effect was partially reversed by miR-223-3p inhibitors(P<0.05). Conclusions STAT1 activated LINC00987 regulates miR-223-3p/FZD4 axis to induce M2-type polarization of GBM-related macrophages.

Key words: glioblastoma, LINC00987, miR-223-3p, polarization of M2 type macrophages

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