Deregulated microRNAs Are Associated with Patient Survival and Predicted to Target Genes That Modulate Lung Cancer Signaling Pathways

SIMPLE SUMMARY: Lung cancer is the leading cause of cancer death, worldwide. The low survival rates are mainly due to disease diagnosis in advanced stages, and the lack of effective treatments. In this study, we analyzed molecules known as microRNAs, which regulate the expression of a large proportion of the human genes. microRNAs are involved in processes related to the development and progression of cancer. In lung cancer, many microRNAs can drive disease. This study showed that some microRNAs have aberrant levels in tumor cells of the two most common types of lung cancer: lung adenocarcinoma and squamous cell carcinoma. In addition, we found that one microRNA, named miR-25-3p, had aberrantly increased levels in tumor cells from patients who died of lung cancer. These results are useful to better understand the biology of lung cancer, and can contribute as an additional tool to predict patient outcome/survival. ABSTRACT: (1) Background: Although the advances in diagnostic and treatment strategies, lung cancer remains the leading cause of cancer-related deaths, worldwide, with survival rates as low as 16% in developed countries. Low survival rates are mainly due to late diagnosis and the lack of effective treatment. Therefore, the identification of novel, clinically useful biomarkers is still needed for patients with advanced disease stage and poor survival. Micro(mi)RNAs are non-coding RNAs and potent regulators of gene expression with a possible role as diagnostic, prognostic and predictive biomarkers in cancer. (2) Methods: We applied global miRNA expression profiling analysis using TaqMan(®) arrays in paired tumor and normal lung tissues (n = 38) from treatment-naïve patients with lung adenocarcinoma (AD; n = 23) and lung squamous cell carcinoma (SCC; n = 15). miRNA target genes were validated using The Cancer Genome Atlas (TCGA) lung AD (n = 561) and lung SCC (n = 523) RNA-Seq datasets. (3) Results: We identified 33 significantly deregulated miRNAs (fold change, FC ≥ 2.0 and p < 0.05) in tumors relative to normal lung tissues, regardless of tumor histology. Enrichment analysis confirmed that genes targeted by the 33 miRNAs are aberrantly expressed in lung AD and SCC, and modulate known pathways in lung cancer. Additionally, high expression of miR-25-3p was significantly associated (p < 0.05) with poor patient survival, when considering both tumor histologies. (4) Conclusions: miR-25-3p may be a potential prognostic biomarker in non-small cell lung cancer. Genes targeted by miRNAs regulate EGFR and TGFβ signaling, among other known pathways relevant to lung tumorigenesis.