MicroRNA 198 Inhibits Invasion and Metastasis in Non-Small Cell Lung Cancer by Targeting Toll-Like Receptor 4

Abstract

The expression of microRNA 198 which is localized in human chromosome 13q13.3 is downregulated in many malignant tumors. The purpose of this study is to investigate the regulatory effects of microRNA 198 on non-small cell lung cancer and the associated regulatory mechanism. The expression levels of microRNA 198 in non-small cell lung cancer cell lines and tumor tissues were determined using the reverse transcription polymerase chain reaction method. Overexpression microRNA in adenocarcinomic human alveolar basal epithelial cells, non-small cell lung cancer cells and cell proliferation in each group were measured with the cell counting kit-8 method. Cell migration was determined with a cell scratch test, while transwell assay was used for the determination of cell migration and invasion capacities. Bioinformatics website was used to predict microRNA 198 target genes and verified with double luciferase assay. Western blot method was used to assay the protein expression level of toll-like receptor 4 in the cells and the effects of overexpression of microRNA 198 on the regulation of cell proliferation and migration by microRNA 198. The expressions of microRNA 198 in non-small cell lung cancer cell lines and tissues were significantly downregulated. However, overexpression of microRNA 198 through transfection significantly inhibited the proliferation, migration and invasion of lung cancer cell lines adenocarcinomic human alveolar basal epithelial cells and non-small cell lung cancer cells and directly targeted and inhibited the expression of toll-like receptor 4. Overexpression of toll-like receptor 4 reversed the regulatory effect of microRNA 198 to some extent. MicroRNA 198 inhibits the proliferation, migration and invasion of non-small cell lung cancer cells by targeting toll-like receptor 4, thereby playing the role of tumor suppressor gene in the development of non-small cell lung cancer.