MiR-203 Enhances Let-7 Biogenesis By Targeting LIN28B To Suppress Tumor Growth In Non-small Cell Lung Cancer

Human cancers often exhibitdecreased microRNA(miRNA)biogenesis and global aberrant expression of miRNAs;thus,targeting the miRNA biogenesis pathway represents a novel strategy for cancer therapy.Here,we report that miR-203 enhances the biogenesis of tumor suppressor let-7 in lung cancer by directly targeting LIN28B.Specially,we found that the LIN28B protein levels were dramatically increased in lung cancer tissues,but its mRNA levels did not differ significantly from nomal tissues,suggesting that a post-transcriptional mechanism is involved in LIN28B regulation.Interestingly,miR-203 overexpression was accompanied by massive upregulation of a group of miRNAs,especially let-7.Besides,the let-7 expression level was concordant with the miR-203 expression in lung cancer tissues,implying that there is a biological relevance between the two.Furthermore,we showed that miR-203 played a critical role of inhibiting the proliferation and promoting the apoptosis in lung cancer cells by suppressing LIN28B and enhancing let-7 biogenesis.In summary,our results establish a novel mechanism that miR-203,LIN28B and let-7 are tightly linked a regulatory network in lung cancer cells.The findings shed light on the role of a specific miRNA as a modulator of miRNA biogenesis and provide basis for developing new strategies for lung cancer therapy.