MicroRNA-140-3p inhibits proliferation and promotes apoptosis in non-small cell lung cancer by targeting MDIG

Background: MicroRNAs (miRNAs) are associated with cancer progression. MiR-140-3p is a tumor suppressor. Nevertheless, its function in non-small cell lung cancer (NSCLC) is unclear.

Methods: MiR-140-3p expression in NSCLC clinical specimens was examined using the TCGA database and real-time PCR. NSCLC cell proliferation and apoptosis were investigated after the miRNA overexpression. Then, mineral dust-induced gene (MDIG) levels in NSCLC clinical specimens were monitored by real-time PCR and western blotting. Bioinformatics predicated the binding of miR-140-3p to MDIG, and their relationship was validated by luciferase reporter assay. The miR-140-3p/MDIG axis was further validated through rescue experiments. The involvement of STAT3 signaling in the actions of miR-140-3p/MDIG axis was investigated.

Results: MiR-140-3p was decreased in NSCLC tissues and negatively correlated with MDIG expression. Additionally, it was also lower in high-grade specimens than in low-grade ones. MiR-140-3p restrained cell proliferation, facilitated apoptosis, and inhibited STAT3 signaling in NSCLC. Interestingly, MDIG was a target of this miRNA. Furthermore, MDIG upregulation abolished miR-140-3p's effect on cell proliferation, apoptosis, and STAT3 pathway in NSCLC cells.

Conclusion: MiR-140-3p restrained NSCLC development through the regulation of the STAT3 pathway by targeting MDIG. This axis may be a promising target for NSCLC treatment.