Signal transducer and activator of transcription 3
RNA sequestering activity
Reciprocal regulation of miR-206 and IL-6/STAT3 pathway mediates IL6-induced gefitinib resistance in EGFR-mutant lung cancer cells.
Persistently activated IL-6/STAT3 pathway promotes acquired resistance to targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC) treatment. miR-206 has been verified to be dysregulated and plays as a negative regulator in lung cancer. However, whether miR-206 may overcome IL6-induced gefitinib resistance in EGFR-mutant lung cancer remains elusive. In this study, we investigated the role of miR-206 in IL6-induced gefitinib-resistant EGFR-mutated lung cancer cell lines. We showed that forced miR-206 expression restored gefitinib sensitivity in IL6-induced gefitinib-resistant EGFR-mutant lung cancer cells by inhibiting IL6/JAK1/STAT3 pathway. Specifically, mechanistic investigations revealed that miR-206 blocked IL-6/STAT3 signalling via directly targeting the 3'-UTR of intracellular IL-6 messenger RNA. Moreover, IL-6 induced miR-206 down-regulation by reducing the cropping process of primary miR-206 (pri-miR-206) into the Drosha/DGCR8 complex. Taken together, our findings reveal a direct role of miR-206 in regulating IL-6/STAT3 pathway and contrarily activated IL-6/STAT3 signalling mediates the miR-206 maturation process in gefitinib-resistant EGFR-mutant lung cancer cells.