Coagulation Factor X Regulated by CASC2c Recruited Macrophages and Induced M2 Polarization in Glioblastoma Multiforme
Authors: Yingnan Sun
Yan Zhang
Xiaoling She
Minghua Wu
Peiyao Li
Qiang Liu
Guiyuan Li
Jianbo Feng
Yang Liu
Chunhua Zhao
Changhong Liu
Haijuan Fu
Zhibin Yu
Qing Liu
Tao Liu
Journal: Frontiers in Immunology (2018)
Discipline: IMMUNOLOGY
Keywords: AKT; extracellular signal-related kinase 1/2; glioblastoma multiforme; polarization; tumor-associated macrophages.
Affiliations: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China., The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China., The Second Xiangya Hospital, Central South University, Changsha, China., The Third Xiangya Hospital, Central South University, Changsha, China., The Xiangya Hospital, Central South University, Changsha, China.

Abstract:  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. 

Retracted: No

PubPeer comments:
 The authors seem to have uploaded the same flow cytometry image twice. Once in Figure 4 and once in Figure 6. ![file] Could the authors check their raw data and contact the journal for corrections? , 
 The authors issued a correction for the flow cytometry image in Figure 4 on May 29, 2020. Information available here: https: www.frontiersin.org articles 10.3389 fimmu.2020.00934 full Perhaps the authors would like to go through *the entirety* of their publication, as there appears to be other image duplications. We could start, for example, with this pair of histology images in Figure 1. ![file] ,