Thyroid cancer is the most common endocrine malignancy, and miR-574 is significantly upregulated in thyroid cancer. However, the role and underlying mechanism of miR-574 in thyroid cancer development are poorly understood. In this study, we showed that NF-κB/p65 signaling pathway was activated and miR-574 was upregulated in thyroid cancer cells. p65 directly bound to the promoter of miR-574 and activated miR-574 transcription. Functionally, miR-574 inhibited apoptosis, promoted proliferation and migration of thyroid cancer cells, and stimulated thyroid cancer-induced tube formation of endothelial cells. On the molecular level, miR-574 inhibited the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) by binding to 3'-UTR of BNIP3. miR-574 also downregulated the expression of apoptosis-inducing factor (AIF), while elevated the levels of MMP2, MMP9, and VEGFA. In vivo, miR-574 promoted xenograft growth, which was associated with reduced apoptosis and enhanced angiogenesis. NF-κB/miR-574 signaling presents multiple oncogenic activities on thyroid cancer development by directly regulating the BNIP3/AIF pathway. Therefore, targeting NF-κB/miR-574 signaling may reduce the aggressiveness of thyroid cancer. IMPLICATIONS: miR-574, directly regulated by NF-κB/p65, promotes tumorigenesis of thyroid cancer via inhibiting BNIP3/AIF pathway.
©2020 American Association for Cancer Research.