miR-194 suppresses high glucose-induced non-small cell lung cancer cell progression by targeting NFAT5

Diabetes mellitus (DM) is linked to an increased risk of lung cancer; however, the exact molecular basis is unclear.

We used a microarray method and found a group of microRNAs differently expressed in lung cancer cells at high or low glucose treatment.

Among these, miR-194 changed significantly, which indicated further analysis. miR-194 was significantly downregulated in non-small cell lung cancer (NSCLC) cells cultured in high glucose (HG) medium and clinical NSCLC tissues with DM. The introduction of miR-194 significantly suppressed the proliferation, migration, and invasion of lung cancer cells induced by HG, suggesting that miR-194 may be a suppressor during HG-induced NSCLC progression. Further analysis indicated that NFAT5 was a direct target gene of miR-194, evidenced by the direct binding of miR-194 with the 3'untranslated region of NFAT5. MiR-194 could decrease the expression of NFAT5 at both messenger RNA and protein levels, while overexpression of NFAT5 reversed the decreased proliferation, migration, and invasion ability mediated by miR-194 in lung cancer cells.

Our findings provide new insight into the mechanism of NSCLC progression. Therapeutically, miR-194 may serve as a potential target for the treatment of lung cancer patients with DM.