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

doi:10.16352/j.issn.1001-6325.2023.07.1060

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

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.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 Lijie^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/Abstract

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

中图分类号:

R979.1

张宝瑞, 马春晓, 秦历杰. 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[J]. 基础医学与临床, 2023, 43(7): 1060-1068.

ZHANG Baorui, MA Chunxiao, QIN Lijie. STAT1-induced LINC00987 regulates miR-223-3p/FZD4 and promotes M2-type polarization of human glioblastoma-associated macrophages[J]. Basic & Clinical Medicine, 2023, 43(7): 1060-1068.

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参考文献

[1] 张宁,马辉辉,王凡,等.脑胶质瘤患者MGMT启动子甲基化和IDH1突变与临床预后相关[J].基础医学与临床,2021,41:1476-1480.
[2] Liu C, Ma Y, Wang R, et al. LINC00987 knockdown inhibits the progression of acute myeloid leukemia by suppressing IGF2BP2-mediated PA2G4 expression[J].Anticancer Drugs, 2022, 33: e207-e217.
[3] Xiao R, Yang M, Tan Y, et al. Identification of five immune-related lncRNAs predicting survival and tumor microenvironment characteristics in breast cancer[J].Comput Math Methods Med, 2021, 2021: 6676692. doi:10.1155/2021/6676692.
[4] Chuang HY, Su YK, Liu HW, et al. Preclinical evidence of STAT3 inhibitor pacritinib overcoming temozolomide resistance via downregulating miR-21-enriched exosomes from M2 glioblastoma-associated macrophages[J]. Journal of Clinical Medicine, 2019, 8:959. doi:10.3390/jcm8070959.
[5] Han L, Li Z, Jiang Y, et al. SNHG29 regulates miR-223-3p/CTNND1 axis to promote glioblastoma progression via Wnt/β-catenin signaling pathway[J].Cancer Cell Int, 2019, 19: 345. doi:10.1186/s12935-019-1057-x.
[6] El-Sehemy A, Selvadurai H, Ortin-Martinez A, et al. Norrin mediates tumor-promoting and -suppressive effects in glioblastoma via Notch and Wnt[J].J Clin Invest, 2020, 130: 3069-3086.
[7] Cai S, Lu JX,Wang YP, et al. SH2B3, transcribed by STAT1, promotes glioblastoma progression through transducing IL-6/gp130 signaling to activate STAT3 signaling[J].Front Cell Dev Biol, 2021, 9: 606527-606527.
[8] 张学政,吴冬冰,张学娟,等.胃癌细胞外泌体lncRNA LOXL1-AS1诱导M2型巨噬细胞极化功能及机制研究[J].现代肿瘤医学,2022,30:1374-1380.
[9] 魏冲,姜志超,王昊天,等.来那度胺可抑制单核细胞向M2型巨噬细胞分化及相关细胞因子的分泌[J].基础医学与临床,2015,35:786-791.
[10] Ding Q, Shen L, Nie X, et al. miR-223-3p overexpression inhibits cell proliferation and migration by regulating inflammation-associated cytokines in glioblastomas[J].Pathol Res Pract, 2018, 214: 1330-1339.
[11] Jin X, Jeon HY, Joo KM, et al. Frizzled 4 regulates stemness and invasiveness of migrating glioma cells established by serial intracranial transplantation[J].Cancer Res, 2011, 71: 3066-3075.

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

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

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