Downregulation of hsa-microRNA-204-5p and identification of its potential regulatory network in non-small cell lung cancer: RT-qPCR, bioinformatic- and meta-analyses

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

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.

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.

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.