miR-98 inhibits expression of TWIST to prevent progression of non-small cell lung cancers.

Evidence is mounting that micro RNAs (miRNAs) play a critical role in tumor development. However, the role of miRNAs in lung cancer progression remains largely unknown. Herein, we found that miR-98 significantly impaired in patients with non-small cell lung cancers (NSCLC) and was a novel regulator of NSCLC progression. Patients with high miR-98 expression had a longer overall survival than with low miR-98 expression (p=0.0495). miR-98 expression level inversely correlated with TWIST mRNA level in 71 clinical tissue specimens of NSCLC (p<0.01). Luciferase assay demonstrated that miR-98 interacted binding sites in the TWIST 3'-UTR and reduced expression of TWIST, resulting in repression of cell migration and invasion via impeding TWIST-mediated EMT. Furthermore, introduction of synthetic miR-98 caused growth arrest by inactivating TWIST-Akt-CDK4/CDK6. Meanwhile, miR-98 mimic induced apoptosis by targeting TWIST-Akt axis. In a conclusion, these observations imply that miR-98 may act as a tumor suppressor in NSCLC to decelerate NSCLC aggressiveness by inhibiting TWIST expression.