MicroRNA-139 Facilitates Non-Small Cell Lung Cancer Progression via Modulating the Epidermal Growth Factor Receptor (EGFR)/Mitogen-Activated Protein Kinase (MEK)/Extracellular Signal-Regulated Kinase (ERK) Signaling Pathway

We aimed to elucidate the role of miR-139 in the progression of non-small cell lung cancer (NSCLC) and its underlying mechanisms. Tumor tissues and paracancerous tissues were collected to obtain NSCLC cells and normal pulmonary epithelial cells, respectively. The expression of miR-139 in tissues and cells were determined via real-time quantitative PCR. The NSCLC cells were transfected with miR-139 inhibitor, siRNA-NC, miR-139 mimics, or vectors, respectively, followed by expression measurement of miR-139 via PCR. Colony formation and CCK-8 assays were employed to assess the cellular proliferation, along with transwell experiment for investigating the tendency of cancer cells in invasion and metastasis. The expression levels of proteins were semi-quantified via Western Blot analysis, including proteins involved in the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway and those related to epithelial-mesenchymal transition (EMT). For rescue experiments, an EGFR agonist was applied to transfect cells, followed by the detection of potentials of cancer cells in proliferation and invasion along with the expression determination of the proteins involved. Eventually, mouse xenograft models were established using cells transfected with miR-139 inhibitor or siRNA-NC, respectively, of which the tumor development was monitored and the expression of EGFR in the tumor tissues of the mouse xenograft models was detected via immunohistochemical staining. A significant increase of miR-139 was detected in NSCLC tissues, of which the elevation was related to the tumor size, malignancy, and poor prognosis. Compared with cells in the control group. miR-139 inhibition enhanced the proliferation of NSCLC cells both in vivo and in vitro, which was accompanied by the suppressed expression of proteins related to the EMT process, along with the enhanced potentials cell invasion and migration. Additionally, miR-139 modulated EGFR expression and activated its signal transduction in EGFR/MEK/ERK pathway to exert its carcinogenic function. MiRNA-139 may facilitate NSCLC progression via modulating the EGFR/MEK/ERK signal-transduction pathway.