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成纤维细胞生长因子 14 在肺腺癌中充当肿瘤抑制因子。

Fibroblast Growth Factor-14 Acts as Tumor Suppressor in Lung Adenocarcinomas.

机构信息

Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.

Institute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, 60590 Frankfurt, Germany.

出版信息

Cells. 2020 Jul 22;9(8):1755. doi: 10.3390/cells9081755.

Abstract

Investigation of the molecular dynamics in lung cancer is crucial for the development of new treatment strategies. Fibroblast growth factor (FGF) 14 belongs to the FGF family, which might play a crucial role in cancer progression. We analyzed lung adenocarcinoma (LUAC) patients samples and found that FGF14 was downregulated, correlating with reduced survival and oncogenic mutation status. FGF14 overexpression in lung cancer cell lines resulted in decreased proliferation, colony formation, and migration, as well as increased expression of epithelial markers and a decreased expression of mesenchymal markers, indicating a mesenchymal to epithelial transition in vitro. We verified these findings using small interfering RNA against FGF14 and further confirmed the suppressive effect of FGF14 in a .- Il2rg/ immunodeficient xenograft tumor model. Moreover, FGF14 overexpressing tumor cell RNA sequencing data suggests that genes affected by FGF14 were related to the extracellular matrix, playing a role in proliferation and migration. Notably, newly identified FGF14 target genes, adenosine deaminase RNA specific B1 (), collagen and calcium-binding epidermal growth factor domain-containing protein 1 (), α1 chain of collagen XI (), and mucin 16 () expression was negatively correlated with overall survival when was downregulated in LUAC. These findings led us to suggest that FGF14 regulates proliferation and migration in LUAC.

摘要

研究肺癌的分子动力学对于开发新的治疗策略至关重要。成纤维细胞生长因子 14(FGF14)属于 FGF 家族,可能在癌症进展中发挥关键作用。我们分析了肺腺癌(LUAC)患者样本,发现 FGF14 下调,与生存时间缩短和致癌突变状态相关。在肺癌细胞系中过表达 FGF14 导致增殖、集落形成和迁移减少,上皮标志物表达增加,间充质标志物表达减少,表明体外发生了间充质到上皮的转变。我们使用针对 FGF14 的小干扰 RNA 验证了这些发现,并进一步在.-Il2rg/免疫缺陷异种移植肿瘤模型中证实了 FGF14 的抑制作用。此外,FGF14 过表达肿瘤细胞的 RNA 测序数据表明,受 FGF14 影响的基因与细胞外基质相关,在增殖和迁移中发挥作用。值得注意的是,新鉴定的 FGF14 靶基因腺苷酸脱氨酶 RNA 特异性 B1 ()、胶原和钙结合表皮生长因子域蛋白 1 ()、胶原 XI 的 α1 链 () 和粘蛋白 16 () 的表达与 LUAC 中的总生存期呈负相关。这些发现使我们认为 FGF14 调节 LUAC 中的增殖和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e9/7466013/d00b6521ee9e/cells-09-01755-g001.jpg

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