Abstract
Tumor-promoting cytokines are a cause of tumor progression; therefore, identifying key regulatory microRNAs (miRNAs) for controlling their production is important. The aim of this study is to identify promising miRNAs associated with tumor-promoting cytokines in non-small cell lung cancer (NSCLC). We identified circulating miRNAs from 16 published miRNA profiles. The selected miRNAs were validated in the serum of 32 NSCLC patients and compared with 33 patients with other lung diseases and 23 healthy persons using quantitative real-time PCR. The cytokine concentration was investigated using the enzyme-linked immunoassay in the same sample set, with clinical validation of the miRNAs. The correlation between miRNA expression and cytokine concentration was evaluated by Spearman's rank correlation. For consistent direction, one up-regulated miRNA (miR-145) was found in four studies, and seven miRNAs were reported in three studies. One miRNA (miR-20a) and four miRNAs (miR-25-3p, miR-223, let-7f, and miR-20b) were reported in six and five studies. However, their expression was inconsistent. In the clinical validation, serum miR-145 was significantly down-regulated, whereas serum miR-20a was significantly up-regulated in NSCLC, compared with controls. Regarding serum cytokine, all cytokines [vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and transforming growth factor β (TGF-β)], except tumor necrosis factor-α (TNF-α), had a higher level in NSCLC patients than controls. In addition, we found a moderate correlation between the TGF-β concentration and miR-20a (r = -0.537, p = 0.002) and miR-223 (r = 0.428, p = 0.015) and a weak correlation between the VEGF concentration with miR-20a (r = 0.376, p = 0.037) and miR-223 (r = -0.355, p = 0.046). MiR-145 and miR-20a are potential biomarkers for NSCLC. In addition, the regulation of tumor-promoting cytokine, through miR-20a and miR-223, might be a new therapeutic approach for lung cancer.
Highlights
Lung cancer is the most common and leading cause of cancer death worldwide, accounting for 11.6% of the total cases and 18.4% of the total cancer deaths in 2018, respectively [1]
Tumor progression is supported by tumor-promoting cytokines, in which high serum levels of several cytokines, such as vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), transforming growth factor β (TGF-β), and tumor necrosis factor-α (TNF-α), are correlated with advanced stages of lung cancer [4, 5]
There has been accumulating evidence to support the regulation of cytokines by miRNAs, studies conducted to determine the association of miRNAs and tumorpromoting cytokines in clinical samples in lung cancer are limited
Summary
Lung cancer is the most common and leading cause of cancer death worldwide, accounting for 11.6% of the total cases and 18.4% of the total cancer deaths in 2018, respectively [1]. Tumor progression is supported by tumor-promoting cytokines, in which high serum levels of several cytokines, such as vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), transforming growth factor β (TGF-β), and tumor necrosis factor-α (TNF-α), are correlated with advanced stages of lung cancer [4, 5]. MiRNAs are short noncoding RNAs, 20–22 nucleotides in length. They suppress gene expression at the post-transcriptional level by binding to the 3’-untranslated regions of mRNAs [6]. There has been accumulating evidence to support the regulation of cytokines by miRNAs, studies conducted to determine the association of miRNAs and tumorpromoting cytokines in clinical samples in lung cancer are limited
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