Coagulation Factor X Regulated by CASC2c Recruited Macrophages and Induced M2 Polarization in Glioblastoma Multiforme

被引:53
作者
Zhang, Yan [1 ,2 ]
Feng, Jianbo [1 ,2 ]
Fu, Haijuan [1 ,2 ]
Liu, Changhong [1 ,2 ]
Yu, Zhibin [1 ,2 ]
Sun, Yingnan [1 ]
She, Xiaoling [3 ]
Li, Peiyao [1 ,2 ]
Zhao, Chunhua [1 ,2 ]
Liu, Yang [1 ,2 ]
Liu, Tao [1 ,2 ]
Liu, Qiang [4 ]
Liu, Qing [5 ]
Liu, Guiyuan [1 ,2 ]
Wu, Minghua [1 ,2 ]
机构
[1] Cent S Univ, Xiangya Med Sch, Affiliated Tumor Hosp, Hunan Prov Tumor Hosp, Changsha, Hunan, Peoples R China
[2] Cent S Univ, Canc Res Inst, Key Lab Carcinogenesis Chinese,Chinese Minist Edu, Key Lab Carcinogenesis & Canc Invas,Minist Hlth, Changsha, Hunan, Peoples R China
[3] Cent S Univ, Xiangya Hosp 2, Changsha, Hunan, Peoples R China
[4] Cent S Univ, Xiangya Hosp 3, Changsha, Hunan, Peoples R China
[5] Cent S Univ, Xiangya Hosp, Changsha, Hunan, Peoples R China
基金
美国国家科学基金会;
关键词
tumor-associated macrophages; polarization; glioblastoma multiforme; extracellular signal-related kinase 1/2; AKT; TUMOR-ASSOCIATED MACROPHAGES; CANCER-CELL MIGRATION; BREAST-CANCER; TISSUE-FACTOR; MICRORNA-338-3P FUNCTIONS; STEM-CELLS; ACTIVATION; GROWTH; INVASION; PROMOTES;
D O I
10.3389/fimmu.2018.01557
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Tumor-associated macrophages (TAMs) constitute a major component of inflammatory cells in the glioblastoma multiforme (GBM) tumor microenvironment. TAMs have been implicated in GBM angiogenesis, invasion, local tumor recurrence, and immunosuppression. Coagulation factor X (FX) is a vitamin K-dependent plasma protein that plays a role in the regulation of blood coagulation. In this study, we first found that FX was highly expressed and positively correlated with TAM density in human GBM. FX exhibited a potent chemotactic capacity to recruit macrophages and promoted macrophages toward M2 subtype polarization, accelerating GBM growth. FX bound to extracellular signal-related kinase (ERK) 1/2 and inhibited p-ERK1/2 in GBM cells. FX was secreted in the tumor microenvironment and increased the phosphorylation and activation of ERK1/2 and AKT in macrophages, which may have been responsible for the M2 subtype macrophage polarization. Moreover, although the lncRNA CASC2c has been verified to function as a miR-101 competing endogenous RNA (ceRNA) to promote miR-101 target genes in GBM cells, we first confirmed that CASC2c did not function as a miR-338-3p ceRNA to promote FX expression, and that FX was a target gene of miR-338-3p. CASC2c interacted with and reciprocally repressed miR-338-3p. Both CASC2c and miR-388-3p bound to FX and commonly inhibited its expression and secretion. CASC2c repressed M2 subtype macrophage polarization. Taken together, our findings revealed a novel mechanism highlighting CASC2c and FX as potential therapeutic targets to improve GBM patients by altering the GBM microenvironment.
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页数:19
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