miR-29a-3p inhibits growth, proliferation, and invasion of papillary thyroid carcinoma by suppressing NF-κB signaling via direct targeting of OTUB2

BACKGROUND: Aberrant expression of microRNAs (miRNAs) is closely involved in cancer development. Downregulation of miR-29a-3p and its tumor suppressive roles in cancer have been revealed by multiple reporters. However, study of its expression pattern and function in papillary thyroid carcinoma (PTC) is rare. MATERIALS AND METHODS: The expression of miR-29a-3p in PTC tissues and cells was detected by qPCR. CCK-8, plate clone formation, transwell invasion, Western blot, immunohistochem-istry, and luciferase reporter assays were carried out to identify the target of miR-29a-3p and explore its roles and mechanisms in PTC. RESULTS: Deregulated miR-29a-3p in PTC tissues and cell lines were revealed by qPCR. Restoring miR-29a-3p expression significantly inhibited growth, proliferation, and invasion of PTC cells demonstrated by CCK-8, plate clone formation, and transwell assays. Luciferase reporter assays showed miR-29a-3p can directly target OTUB2 in PTC cells. Ectopic expression of OTUB2 can antagonize the effects of miR-29a-3p on cell growth, proliferation, and invasion of PTC. Mechanistically, OTUB2 overexpression can activate NF-κB signaling mostly by stabilizing TRAF6. Upregulated OTUB2 expression was observed in PTC tissues via immunohistochemistry analysis. Moreover, OTUB2 showed a positive correlation to metastatic status and showed a negative correlation to the overall survival rate in PTC patients. CONCLUSION: Deregulated miR-29a-3p can promote cell growth, proliferation, and invasion in PTC. OTUB2 is a direct downstream target of miR-29a-3p in PTC, and it mediates the effects of deregulated miR-29a-3p by activating TRAF6-associated NF-κB signaling in PTC.