Background. miR-139-5p is lowly expressed in various human cancers and exerts its antitumor effect through different molecular mechanisms, yet the molecular mechanism of miR-139-5p in lung adenocarcinoma (LUAD) remains to be further elucidated. The study is aimed at investigating the role and the regulatory mechanism of miR-139-5p in LUAD progression. Methods. Differential analysis was performed on miRNA expression data in the TCGA-LUAD dataset. qRT-PCR was employed to detect the transcription levels of miR-139-5p and MAD2L1 in LUAD cells, while western blot was carried out for the detection of MAD2L1 protein expression. CCK-8 and Transwell assays were implemented to assess LUAD cell proliferation, migration, and invasion. A dual-luciferase reporter gene assay was conducted to verify the direct targeting relationship between miR-139-5p and MAD2L1. Results. miR-139-5p was significantly downregulated in LUAD cells in comparison with that in human normal bronchial epithelial cells. Overexpressing miR-139-5p inhibited LUAD cell proliferation, migration, and invasion, while opposite results could be observed when miR-139-5p was inhibited. MAD2L1 was identified as a direct target of miR-139-5p in LUAD. Besides, the inhibitory effect of miR-139-5p overexpression on LUAD cell proliferation, migration, and invasion was attenuated by overexpressing MAD2L1. Conclusion. Our study suggests that miR-139-5p is lowly expressed in LUAD cells and inhibits LUAD cell proliferation, migration, and invasion by targeted suppressing MAD2L1 expression. It is of potential significance for the prognosis and treatment of LUAD.

中文翻译：

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miR-139-5p 通过靶向 MAD2L1 抑制肺腺癌细胞增殖、迁移和侵袭

背景。miR-139-5p在多种人类癌症中低表达，并通过不同的分子机制发挥抗肿瘤作用，但miR-139-5p在肺腺癌（LUAD）中的分子机制仍有待进一步阐明。本研究旨在探讨miR-139-5p在LUAD进展中的作用及调控机制。方法。对 TCGA-LUAD 数据集中的 miRNA 表达数据进行差异分析。qRT-PCR检测LUAD细胞中miR-139-5p和MAD2L1的转录水平，Western blot检测MAD2L1蛋白表达。采用 CCK-8 和 Transwell 检测来评估 LUAD 细胞增殖、迁移和侵袭。进行双荧光素酶报告基因测定以验证 miR-139-5p 和 MAD2L1 之间的直接靶向关系。结果。与人正常支气管上皮细胞相比，miR-139-5p 在 LUAD 细胞中显着下调。过表达miR-139-5p抑制LUAD细胞增殖、迁移和侵袭，而抑制miR-139-5p时可以观察到相反的结果。MAD2L1 被确定为 LUAD 中 miR-139-5p 的直接靶标。此外，过表达MAD2L1会减弱miR-139-5p过表达对LUAD细胞增殖、迁移和侵袭的抑制作用。结论。我们的研究表明，miR-139-5p 在 LUAD 细胞中低表达，并通过靶向抑制 MAD2L1 表达来抑制 LUAD 细胞增殖、迁移和侵袭。对于LUAD的预后和治疗具有潜在意义。