Abstract
The lack of a useful biomarker partly contributes to the increased mortality of non-small cell lung cancer (NSCLC). MiRNAs have become increasingly appreciated in diagnosis of NSCLC. In the present study, we used microarray to screen 2,549 miRNAs in serum samples from the training cohort (NSCLC, n = 10; the healthy, n = 10) to discover differentially expressed miRNAs (DEMs). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was applied to validate the expression level of selected overexpressed DEMs of NSCLC in a validation cohort (NSCLC, n = 30; the healthy, n = 30). Area under the receiver operating characteristic curve (AUC) was performed to evaluate diagnostic capability of the DEMs. The expression of the miRNAs in tissues was analyzed based on the TCGA database. Subsequently, the target genes of the miR-4687-3p were predicted by TargetScan. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were tested by R software (ClusterProfiler package). NSCLC cells were transfected with inhibitor or mimic to down-regulate or up-regulate the miR-4687-3p level. The function of miR-4687-3p on proliferation, invasion, and migration of lung cancer cells were investigated through CCK-8 and Transwell assays, respectively. In the results, we identified serum miR-4687-3p that provided a high diagnostic accuracy of NSCLC (AUC = 0.679, 95%CI: 0.543–0.815) in the validation cohort. According to the TCGA database, we found that the miR-4687-3p level was significantly higher in NSCLC tissues than in normal lung tissues (p < 0.05). GO and KEGG pathway enrichment analysis showed that postsynaptic specialization and TGF-β signaling pathway were significantly enriched. Down-regulation of miR-4687-3p could suppress the proliferation, invasion, and migration of the NSCLC cells, compared with inhibitor negative control (NC). Meanwhile, overexpression of miR-4687-3p could promote the proliferation, invasion, and migration of the NSCLC cells compared with mimic NC. As a conclusion, our study first discovered that serum miR-4687-3p might have clinical potential as a non-invasive diagnostic biomarker for NSCLC and play an important role in the development of NSCLC.
Highlights
Lung cancer is the most common malignancy and the leading cause of malignancy-related death in the world, with an estimated 2.3 million new cases and 1.4 million deaths (Siegel and Miller, 2019)
Expression of the selected six individual miRNAs according to the training cohort (Figure 3A) was evaluated with qRT-PCR in 60 serum samples (NSCLC, n = 30; the healthy, n = 30) (Figure 3B)
We compared the expression of tissue miR-4687-3p in non-small cell lung cancer (NSCLC) and the healthy based on the The Cancer Genome Atlas (TCGA) database
Summary
Lung cancer is the most common malignancy and the leading cause of malignancy-related death in the world, with an estimated 2.3 million new cases and 1.4 million deaths (Siegel and Miller, 2019). In terms of the pathological type, non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer. Exploring early detection methods for NSCLC is crucial to reduce NSCLC-related deaths. MiRNA could be released by cancer cells into serum, plasma, or other body fluids to a participant in carcinogenesis, which have been reported in multiple cancers, such as hepatoma carcinoma, NSCLC (Zhang et al, 2015; Zhao et al, 2016; Usuba et al, 2019; Valihrach et al, 2019). Several serum miRNAs with differential expression in patients with NSCLC and the healthy were reported recently, such as miR-16 (Fan et al, 2016), miR-504 (Szpechcinski et al, 2019), and miR-21 (Zhao et al, 2015). Most previous studies merely expound the differential expression of the miRNA in NSCLC and the healthy, but rarely explore the biological function of the miRNA in NSCLC.
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