Department of Otolaryngology, First Hospital of Ningbo City, Ningbo, Zhejiang, 315000, People's Republic of China.
Eur Arch Otorhinolaryngol. 2021 May;278(5):1523-1535. doi: 10.1007/s00405-021-06636-5. Epub 2021 Feb 7.
MiR-4497 has been previously proved to exert an anti-cancer role in laryngeal squamous cell carcinoma (LSCC) by negatively regulating gastrulation brain homeobox 2 (GBX2). However, the mechanism of miR-4497 in LSCC has yet to be fully elucidated. This study intended to investigate the role of FEZF1-AS1 in the migration and invasion of LSCC cells and clarified its mechanism through miR-4497 and GBX2.
qPCR evaluated the expression of FEZF1-AS1, miR-4497 and GBX2 in LSCC tissues and cells, compared with controls. Western blotting analyzed GBX2, E-cadherin, N-cadherin and Vimentin. CCK8, wound healing and transwell assays assessed the viability, migration and invasion of TU686 and UM-SCC-17A cells. Luciferase reporter assay affirmed the interplay of miR-4497 with FEZF1-AS1 or GBX2 and Pearson's correlation analysis explored the association between each two genes in both tumor and non-tumor tissues.
FEZF1-AS1 was highly expressed in LSCC tissues and cells. Silence or elevation of FEZF1-AS1 inhibited or promoted the migration and invasion of TU686 and UM-SCC-17A cells. FEZF1-AS1 targeted and negatively modulated miR-4497. Inhibition of miR-4497 markedly restored the FEZF1-AS1 silence-repressed cell viability of TU686 and UM-SCC-17A cells. Further, FEZF1-AS1 could positively regulate GBX2 via negative regulation of miR-4497. In these two cells, GBX2 deficiency reversed the promoting impacts of miR-4497 repression on migration and invasion.
Taken together, FEZF1-AS1, heightened in LSCC tissues and cells, promotes cell migration and invasion of LSCC cells via targeting miR-4497 that inhibits GBX2. The finding may offer new options for the treatment of this cancer.
miR-4497 通过负向调控原肠胚形成脑同源盒 2（GBX2），已被证实对喉鳞状细胞癌（LSCC）具有抗癌作用。然而，miR-4497 在 LSCC 中的作用机制尚未完全阐明。本研究旨在探讨 FEZF1-AS1 在 LSCC 细胞迁移和侵袭中的作用，并通过 miR-4497 和 GBX2 阐明其机制。
qPCR 检测 LSCC 组织和细胞中 FEZF1-AS1、miR-4497 和 GBX2 的表达情况，并与对照组进行比较。Western blot 分析 GBX2、E-钙黏蛋白、N-钙黏蛋白和波形蛋白。CCK8、划痕愈合和 Transwell 实验评估 TU686 和 UM-SCC-17A 细胞的活力、迁移和侵袭。荧光素酶报告实验证实 miR-4497 与 FEZF1-AS1 或 GBX2 的相互作用，Pearson 相关分析探讨肿瘤和非肿瘤组织中两个基因之间的关联。
FEZF1-AS1 在 LSCC 组织和细胞中高表达。沉默或上调 FEZF1-AS1 抑制或促进了 TU686 和 UM-SCC-17A 细胞的迁移和侵袭。FEZF1-AS1 靶向并负调控 miR-4497。抑制 miR-4497 显著恢复了 TU686 和 UM-SCC-17A 细胞中 FEZF1-AS1 沉默抑制的细胞活力。此外，FEZF1-AS1 可以通过负向调控 miR-4497 来正向调节 GBX2。在这两种细胞中，GBX2 的缺失逆转了 miR-4497 抑制对迁移和侵袭的促进作用。
综上所述，在 LSCC 组织和细胞中高度表达的 FEZF1-AS1 通过靶向 miR-4497 抑制 GBX2 促进 LSCC 细胞的迁移和侵袭。这一发现可能为治疗这种癌症提供新的选择。
