BACKGROUND Pulmonary malignant neoplasms have a high worldwide morbidity and mortality, so the study of these malignancies using microRNAs (miRNAs) has attracted great interest and enthusiasm. The aim of this study was to determine the clinical effect of hsa-microRNA-204-5p (miR-204-5p) and its underlying molecular mechanisms in non-small cell lung cancer (NSCLC). METHODS Expression of miR-204-5p was investigated by real-time quantitative PCR (RT-qPCR). After data mining from public online repositories, several integrative assessment methods, including receiver operating characteristic (ROC) curves, hazard ratios (HR) with 95% confidence intervals (95% CI), and comprehensive meta-analyses, were conducted to explore the expression and clinical utility of miR-204-5p. The potential objects regulated and controlled by miR-204-5p in the course of NSCLC were identified by estimated target prediction and analysis. The regulatory network of miR-204-5p, with its target genes and transcription factors (TFs), was structured from database evidence and literature references. RESULTS The expression of miR-204-5p was downregulated in NSCLC, and the downtrend was related to gender, histological type, vascular invasion, tumor size, clinicopathologic grade and lymph node metastasis (P<0.05). MiR-204-5p was useful in prognosis, but was deemed unsuitable at present as an auxiliary diagnostic or prognostic risk factor for NSCLC due to the lack of statistical significance in meta-analyses and absence of large-scale investigations. Gene enrichment and annotation analyses identified miR-204-5p candidate targets that took part in various genetic activities and biological functions. The predicted TFs, like MAX, MYC, and RUNX1, interfered in regulatory networks involving miR-204-5p and its predicted hub genes, though a modulatory loop or axis of the miRNA-TF-gene that was out of range with shortage in database prediction, experimental proof and literature confirmation. CONCLUSIONS The frequently observed decrease in miR-204-5p was helpful for NSCLC diagnosis. The estimated target genes and TFs contributed to the anti-oncogene effects of miR-204-5p.

中文翻译：

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hsa-microRNA-204-5p的下调及其在非小细胞肺癌中的潜在调控网络的鉴定：RT-qPCR，生物信息学和荟萃分析。

背景技术肺恶性肿瘤在世界范围内具有很高的发病率和死亡率，因此使用microRNA（miRNA）对这些恶性肿瘤的研究引起了极大的兴趣和热情。这项研究的目的是确定非小细胞肺癌（NSCLC）中hsa-microRNA-204-5p（miR-204-5p）的临床作用及其潜在分子机制。方法采用实时定量PCR（RT-qPCR）研究miR-204-5p的表达。在从公共在线存储库中挖掘数据之后，进行了几种综合评估方法，包括接收者操作特征（ROC）曲线，具有95％置信区间（95％CI）的危险比（HR）和综合的荟萃分析，以探讨该表达方式和miR-204-5p的临床应用。通过估计目标预测和分析，确定了miR-204-5p在非小细胞肺癌过程中调控的潜在目标。miR-204-5p的调控网络及其靶基因和转录因子（TFs）由数据库证据和文献参考构成。结果NSCLC中miR-204-5p的表达下调，其下降趋势与性别，组织学类型，血管浸润，肿瘤大小，临床病理分级和淋巴结转移有关（P <0.05）。MiR-204-5p可用于预后，但由于在荟萃分析中缺乏统计学意义且缺乏大规模研究，因此目前不适合作为NSCLC的辅助诊断或预后危险因素。基因富集和注释分析确定了参与各种遗传活动和生物学功能的miR-204-5p候选靶标。预测的TF，例如MAX，MYC和RUNX1，干扰了涉及miR-204-5p及其预测的中枢基因的调控网络，尽管miRNA-TF基因的调节环或轴超出了范围，数据库不足预测，实验证明和文献证实。结论经常观察到的miR-204-5p下降有助于NSCLC诊断。估计的靶基因和TF有助于miR-204-5p的抗癌基因作用。尽管miRNA-TF基因的调节环或轴超出了范围，但缺乏数据库预测，实验证明和文献证实。结论经常观察到的miR-204-5p下降有助于NSCLC诊断。估计的靶基因和TF有助于miR-204-5p的抗癌基因作用。尽管miRNA-TF基因的调节环或轴超出了范围，但缺乏数据库预测，实验证明和文献证实。结论经常观察到的miR-204-5p下降有助于NSCLC诊断。估计的靶基因和TF有助于miR-204-5p的抗癌基因作用。