Formin-like 1 (FMNL1) Is Associated with Glioblastoma Multiforme Mesenchymal Subtype and Independently Predicts Poor Prognosis
Formin-like 1 (FMNL1) Is Associated with Glioblastoma Multiforme Mesenchymal Subtype and Independently Predicts Poor Prognosis
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DOI：
10.3390/ijms20246355
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发表时间：
2019-12-01
影响因子：
5.6
通讯作者：
Arita, Kazunori
中科院分区：
文献类型：
--
作者：
Higa, Nayuta;Shinsato, Yoshinari;Arita, Kazunori
多形性胶质母细胞瘤（GBM）是成人中最常见的原发性恶性脑肿瘤，其特征在于快速增殖、侵袭性迁移和侵入正常脑组织。成形素蛋白质已涉及这些过程。然而，福明样1（FMNL 1）在癌症中的作用仍不清楚。我们研究了FMNL 1表达胶质母细胞瘤样本使用免疫组织化学。我们试图分析FMNL 1表达、临床病理变量和患者生存率之间的相关性。迁移和侵袭试验用于验证FMNL 1对胶质母细胞瘤细胞系的作用。从癌症基因组图谱下载微阵列数据，并使用基因集富集分析（GSEA）进行分析。FMNL 1是217例多形性胶质母细胞瘤患者预后不良的独立预测因子（p < 0.001）。FMNL 1在间充质亚型中的表达显著较高。FMNL 1上调和下调分别与GSEA中的间充质和前神经标记物相关。这些数据突出了FMNL 1在神经间质转化中的重要作用。相反，FMNL 1下调抑制多形性胶质母细胞瘤细胞的迁移和侵袭，分别通过DIAPH 1和GOLGA 2。FMNL 1下调也抑制肌动蛋白纤维组装，诱导形态学变化，并减少丝状肌动蛋白。FMNL 1是一个有前途的治疗靶点，也是GBM进展的有用生物标志物。
Glioblastoma multiforme (GBM), the most common primary malignant brain tumor in adults, is characterized by rapid proliferation, aggressive migration, and invasion into normal brain tissue. Formin proteins have been implicated in these processes. However, the role of formin-like 1 (FMNL1) in cancer remains unclear. We studied FMNL1 expression in glioblastoma samples using immunohistochemistry. We sought to analyze the correlation between FMNL1 expression, clinicopathologic variables, and patient survival. Migration and invasion assays were used to verify the effect of FMNL1 on glioblastoma cell lines. Microarray data were downloaded from The Cancer Genome Atlas and analyzed using gene set enrichment analysis (GSEA). FMNL1 was an independent predictor of poor prognosis in a cohort of 217 glioblastoma multiforme cases (p < 0.001). FMNL1 expression was significantly higher in the mesenchymal subtype. FMNL1 upregulation and downregulation were associated with mesenchymal and proneural markers in the GSEA, respectively. These data highlight the important role of FMNL1 in the neural-to-mesenchymal transition. Conversely, FMNL1 downregulation suppressed glioblastoma multiforme cell migration and invasion via DIAPH1 and GOLGA2, respectively. FMNL1 downregulation also suppressed actin fiber assembly, induced morphological changes, and diminished filamentous actin. FMNL1 is a promising therapeutic target and a useful biomarker for GBM progression.