MicroRNA-218-5p affects lung adenocarcinoma progression through targeting endoplasmic reticulum oxidoreductase 1 alpha

Lung adenocarcinoma (LUAD) severely threatens the health of people owing to its lethality. Nonetheless, the underlying mechanisms on LUAD development remain unclear to a great extent. This work aimed to probe the functions of miR-218-5p in LUAD. MiR-218-5p and endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) were screened as differently downregulated and upregulated RNAs in LUAD, respectively, by bioinformatics analyses. The results of cell functional assays stated that enforced expression of miR-218-5p notably restrained cell viability, invasion, and migration in LUAD. MiR-218-5p may interact with 3’-untranslated region of ERO1A mRNA as analyzed by bioinformatics. Afterward, western blot and dual-luciferase reporter gene analyses were introduced to identify their interaction. ERO1A overexpression reversed the suppressive impacts of miR-218-5p on LUAD cell progression, indicating the implication of miR-218-5p/ERO1A axis in suppressing cancer development. We also observed that this regulatory axis suppressed angiogenesis in LUAD. Taken together, miR-218-5p/ERO1A axis exerted an imperative role in LUAD cell progression, which provides a valuable clue for the development of LUAD therapeutic regimen.

肺腺癌（Lung adenocarcinoma, LUAD）因其高致死性严重威胁人类健康，但其发生发展的潜在机制在很大程度上仍未明确。本研究旨在探究微小RNA miR-218-5p在肺腺癌中的功能。通过生物信息学分析，筛选得到在肺腺癌中表达显著下调的miR-218-5p，以及表达显著上调的内质网氧化还原酶1α（ERO1A）。细胞功能实验结果显示，过表达miR-218-5p可显著抑制肺腺癌细胞的活力、侵袭与迁移能力。生物信息学分析提示，miR-218-5p可与ERO1A mRNA的3'-非翻译区相结合。随后通过蛋白质印迹（Western blot）与双荧光素酶报告基因实验验证了二者的靶向结合关系。ERO1A过表达可逆转miR-218-5p对肺腺癌细胞进程的抑制作用，表明miR-218-5p/ERO1A调控轴在抑制癌症发展中发挥重要作用。本研究还发现该调控轴可抑制肺腺癌的血管生成。综上，miR-218-5p/ERO1A调控轴在肺腺癌细胞进程中发挥关键作用，为肺腺癌治疗方案的开发提供了有价值的线索。