Mechanism of Action of microRNA-146a on Lung Cancer Cells through Notch1/Hes-1 Signaling Pathway.

Abstract

Objective: We explored the mechanism of action of microRNA-146a in the lung cancer cell line A549 through the Noth1/Hes-1 signal pathway.

Methods: A549 cells were divided into a control NT group without transfection, NC group with transfection of miR-146a-NC, and MM group with transfection of miR-146a mimics. We employed qRT-PCR, MTT, Hoechst33258 fluorescence staining, Transwell assay, cell wound scratch assay, and Western blot for detection of the expression of miR-146a and Notch1/Hes-1, cell activity, apoptotic capacity, and invasion and migration abilities.

Results: The expression of miR-146a in MM group was the highest, illustrating transfection was successful. The expression of Notch1 and Hes-1 mRNA in MM group was reduced compared to in the NC and NT groups (P<0.05). The activity of Notch1 and Hes-1 were reduced by transfection of miR-146a as documented by the double luciferase reporter gene assay (P<0.05). The cellular activity in the MM group was lowest after the 48 hours of culture. There was a significant difference compared with the other two groups (P<0.05). Cell activity in the three groups after the 96 hours of culture was higher than after the 72 hours and 48 hours of culture equally (P<0.05).

Conclusion: The low expression of miR-146a could have tumor-prompting action on human NSCLC cells. Up-regulation of the expression of miR-146a restrained biological behaviors such as cell apoptosis and migration through targeted regulation involving the signal pathway of Noth1/Hes-1.