BACKGROUND MiR-182-5p, a cancer-related microRNA (miRNA), modulates tumorigenesis and patient outcomes in various human malignances. This study interroted the clinicopathological significance and molecular mechanisms of miR-182-5p in non-small cell lung cancer (NSCLC). METHODS The clinical significance of miR-182-5p in NSCLC subtypes was determined based on an analysis of 124 samples (lung adenocarcinomas [LUADs], n = 101; lung squamous cell carcinomas [LUSCs], n = 23) obtained from NSCLC patients and paired noncancer tissues and an analysis of data obtained from public miRNA-seq database, miRNA-chip database, and the scientific literature. The NSCLC samples (n = 124) were analyzed using the real-time quantitative polymerase chain reaction (RT-qPCR). Potential targets of miR-182-5p were identified using lists generated by miRWalk v.2.0, a comprehensive atlas of predicted and validated targets of miRNA-target interactions. Molecular events of miR-182-5p in NSCLC were unveiled based on a functional analysis of candidate targets. The association of miR-182-5p with one of the candidate target genes, homeobox A9 (HOXA9), was validated using in-house RT-qPCR and dual-luciferase reporter assays. RESULTS The results of the in-house RT-qPCR assays analysis of data obtained from public miRNA-seq databases, miRNA-chip databases, and the scientific literature all supported upregulation of the expression level of miR-182-5p level in NSCLC. Moreover, the in-house RT-qPCR data supported the influence of upregulated miR-182-5p on malignant progression of NSCLC. In total, 774 prospective targets of miR-182-5p were identified. These targets were mainly clustered in pathways associated with biological processes, such as axonogenesis, axonal development, and Ras protein signal transduction, as well as pathways involved in axonal guidance, melanogenesis, and longevity regulation, in multiple species. Correlation analysis of the in-house RT-qPCR data and dual-luciferase reporter assays confirmed that HOXA9 was a direct target of miR-182-5p in NSCLC. CONCLUSIONS The miR-182-5p expression level was upregulated in NSCLC tissues. MiR-182-5p may exert oncogenic influence on NSCLC through regulating target genes such as HOXA9.

中文翻译：

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非小细胞肺癌中的MiR-182-5p及其靶点HOXA9：结合RT-qPCR，miRNA-seq和miRNA芯片的临床和临床研究。

背景技术MiR-182-5p是一种与癌症相关的microRNA（miRNA），可调节各种人类恶性肿瘤的发生和患者预后。这项研究交错了miR-182-5p在非小细胞肺癌（NSCLC）中的临床病理学意义和分子机制。方法通过对从NSCLC患者和患者中获得的124份样本（肺腺癌[LUADs]，n = 101；肺鳞癌[LUSCs]，n = 23）进行分析，确定miR-182-5p在NSCLC亚型中的临床意义。配对的非癌组织，以及对从公共miRNA-seq数据库，miRNA-芯片数据库和科学文献中获得的数据的分析。使用实时定量聚合酶链反应（RT-qPCR）分析了NSCLC样本（n = 124）。使用miRWalk v.2.0生成的列表确定了miR-182-5p的潜在靶标，关于miRNA与靶标相互作用的预测和验证靶标的全面地图集。基于候选靶标的功能分析，揭示了NSCLC中miR-182-5p的分子事件。miR-182-5p与候选靶基因之一同源盒A9（HOXA9）的关联已通过内部RT-qPCR和双荧光素酶报告基因检测方法进行了验证。结果对从公共miRNA-seq数据库，miRNA芯片数据库和科学文献中获得的数据进行的内部RT-qPCR分析结果均支持NSCLC中miR-182-5p表达水平的上调。此外，内部RT-qPCR数据支持miR-182-5p上调对NSCLC恶性进展的影响。总共确定了774个miR-182-5p预期目标。这些靶标主要集中在与多种物种的生物学过程相关的途径中，例如轴突发生，轴突发育和Ras蛋白信号转导，以及涉及轴突指导，黑色素生成和长寿调节的途径。内部RT-qPCR数据和双荧光素酶报告基因分析的相关性分析证实，HOXA9是NSCLC中miR-182-5p的直接靶标。结论NSCLC组织中miR-182-5p表达水平上调。MiR-182-5p可能通过调节靶基因如HOXA9对NSCLC产生致癌作用。内部RT-qPCR数据和双荧光素酶报告基因分析的相关性分析证实，HOXA9是NSCLC中miR-182-5p的直接靶标。结论NSCLC组织中miR-182-5p表达水平上调。MiR-182-5p可能通过调节靶基因如HOXA9对NSCLC产生致癌作用。内部RT-qPCR数据和双荧光素酶报告基因分析的相关性分析证实，HOXA9是NSCLC中miR-182-5p的直接靶标。结论NSCLC组织中miR-182-5p表达水平上调。MiR-182-5p可能通过调节靶基因如HOXA9对NSCLC产生致癌作用。