Abstract
BackgroundNon-small cell lung cancer (NSCLC) has led to the highest cancer-related mortality for decades. To enhance the efficiency of early diagnosis and therapy, more efforts are urgently needed to reveal the origins of NSCLC. In this study, we explored the effect of miR-542-5p in NSCLC with clinical samples and in vivo models and further explored the prospective function of miR-542-5p though bioinformatics methods.MethodsA total of 125 NSCLC tissue samples were collected, and the expression of miR-542-5p was detected by qRT-PCR. The relationship between miR-542-5p level and clinicopathological features was analyzed. The effect of miR-542-5p on survival time was also explored with K-M survival curves and Cox’s regression. The effect of miR-542-5p on the tumorigenesis of NSCLC was verified with a chick chorioallantoic membrane (CAM) model. The potential target genes were predicted by bioinformatics tools, and relevant pathways were analyzed by GO and KEGG. Several hub genes were validated by Proteinatlas.ResultsThe expression of miR-542-5p was down-regulated in NSCLC tissues, and consistent results were also found in the subgroups of adenocarcinoma and squamous cell carcinoma. Down-regulation of miR-542-5p was found to be connected with advanced TNM stage, vascular invasion, lymphatic metastasis and EGFR. Survival analyses showed that patients with lower miR-542-5p levels had markedly poorer prognosis. Both tumor growth and angiogenesis were significantly suppressed by miR-542-5p mimic in the CAM model. The potential 457 target genes of miR-542-5p were enriched in several key cancer-related pathways, such as morphine addiction and the cAMP signaling pathway from KEGG. Interestingly, six genes (GABBR1, PDE4B, PDE4C, ADCY6, ADCY1 and GIPR) from the cAMP signaling pathway were confirmed to be overexpressed in NSCLCs tissues.ConclusionsThis evidence suggests that miR-542-5p is a potential tumor-suppressed miRNA in NSCLC, which has the potential to act as a diagnostic and therapeutic target of NSCLC.
Highlights
Non-small cell lung cancer (NSCLC) has led to the highest cancer-related mortality for decades
We found that miR-30a [10], miR-193a-3p and miR-133a-3p were down-regulated in NSCLC tissues [11, 12], and all of them have an effect on survival time of patients
The expression of miR-542-5p in NSCLC tissues MiR-542-5p showed lower expression in NSCLC when compared to adjacent normal lung tissues, and consistent results were found in the subgroups of Lung adenocarcinoma (LUAD) and Lung squamous cell carcinoma (LUSC) (Fig. 1a–c)
Summary
Non-small cell lung cancer (NSCLC) has led to the highest cancer-related mortality for decades. Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancer with high mortality worldwide [1]. The study of molecular targeted therapies is progressing, including EGFR and ALK-targeted therapies in lung adenocarcinoma, which have had a successful beginning, they are efficient in just 20% of patients [4]. Given these results, high-performance biological markers are critically needed to find and diagnose NSCLC in early stages, to prevent NSCLC from advancing, and to help advanced patients achieve a better prognosis
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