Background

Long non-coding RNAs (lncRNAs) participate in the initiation and progression of oral squamous cell carcinoma (OSCC). Although lncRNA LINC00174 plays key roles in multiple cancers, its function in OSCC has not yet been reported. This study aimed to clarify LINC00174 function and mechanism of action in OSCC.

Methods

Expression analyses of LINC00174, miR-486-5p, and EIF5A2 mRNA were performed using RT-qPCR. EIF5A2 protein levels were quantified using western blot. Cell growth was investigated by performing CCK-8 and colony formation assays. Cell migration was investigated using wound healing assays. In vivo tumor formation and growth were determined by establishing animal models. The putative binding association between miR-486-5p and LINC00174 or EIF5A2 was verified using dual-luciferase or RIP assays.

Results

LINC00174 and EIF5A2 were overexpressed, while miR-486-5p was poorly expressed in OSCC. Knockdown of LINC00174 expression in OSCC cells impaired proliferation, colony formation, and migration. In animal models, too, LINC00174 absence decelerated tumor development. Further mechanistic investigation showed that LINC00174 acted as a functional sponge of miR-486-5p and that miR-486-5p directly regulated the expression level of downstream EIF5A2. Likewise, miR-486-5p depletion attenuated the inhibitory effects of LINC00174 or EIF5A2 knockdown on OSCC cell malignancy due to their targeting relationship.

Conclusion

LINC00174 is a driving factor in OSCC development by sponging miR-486-5p to regulate EIF5A2 expression. The LINC00174/miR-486-5p/EIF5A2 axis in OSCC, which is revealed in this study, may provide a new molecular network for understanding OSCC pathogenesis.

中文翻译：

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LINC00174 靶向 miR-486-5p/EIF5A2 是口腔鳞状细胞癌的致癌驱动因素

背景

长非编码RNA (lncRNA) 参与口腔鳞状细胞癌(OSCC) 的发生和进展。尽管lncRNA LINC00174在多种癌症中发挥关键作用，但其在OSCC中的功能尚未有报道。本研究旨在阐明 LINC00174 在 OSCC 中的功能和作用机制。

方法

使用 RT-qPCR 对 LINC00174、miR-486-5p 和 EIF5A2 mRNA 进行表达分析。使用蛋白质印迹对 EIF5A2 蛋白水平进行定量。通过进行 CCK-8 和集落形成测定来研究细胞生长。使用伤口愈合测定来研究细胞迁移。通过建立动物模型来确定体内肿瘤的形成和生长。使用双荧光素酶或 RIP 测定验证了 miR-486-5p 与 LINC00174 或 EIF5A2 之间推定的结合关联。

结果

LINC00174 和 EIF5A2 在 OSCC 中过表达，而 miR-486-5p 表达较差。OSCC 细胞中 LINC00174 表达的敲低会损害增殖、集落形成和迁移。在动物模型中，LINC00174 的缺失也会减缓肿瘤的发展。进一步的机制研究表明，LINC00174充当miR-486-5p的功能海绵，并且miR-486-5p直接调节下游EIF5A2的表达水平。同样，由于其靶向关系，miR-486-5p 缺失减弱了 LINC00174 或 EIF5A2 敲低对 OSCC 细胞恶性肿瘤的抑制作用。

结论

LINC00174 通过海绵 miR-486-5p 来调节 EIF5A2 表达，是 OSCC 发展的驱动因子。本研究揭示的 OSCC 中的 LINC00174/miR-486-5p/EIF5A2 轴可能为理解 OSCC 发病机制提供新的分子网络。