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Significance The QKI-5 is a major isoform of QKIs and exerts tumor-suppressive functions in non-small cell lung cancer (NSCLC). MicroRNA dysregulation occurs frequently in cancers, and miR-196b-5p has been reported to have dual functions in NSCLC. We found that miR-196b-5p was up-regulated in NSCLC and was negatively regulated by QKI-5. We demonstrated that miR-196b-5p promoted cellular migration, proliferative ability, and tumor growth both in vitro and in vivo by directly targeting the tumor suppressors, GATA6 and TSPAN12. QKI-5 bound to miR-196b-5p and reduced its stability, thus inhibiting miR-196b-5p expression. In addition, up-regulated miR-196b-5p expression in NSCLC was partially controlled by hypomethylation of its promoter region. Our study suggests that the QKI5∼miR-196b-5p∼GATA6/TSPAN12 pathway might be a promising therapeutic strategy in treating NSCLC.

miR-196b-5p–mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer