Background
Recent studies have proven that abnormal expression of long noncoding RNAs (lncRNAs) often contributes to growth and invasion of cancer cells. The
Conclusions
SOX2-OT downregulation limited PCa cell growth and metastasis by regulating miR-452-5p/HMGB3 axis and inactivating Wnt/β-catenin signaling pathway, which might offer lncRNA-directed diagnosis and therapy for PCa.
Methods
The expression of SOX2-OT, microRNA-452-5p (miR-452-5p), and high mobility group box 3 (HMGB3) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was performed to determine the cell cycle distribution. Western blot assay was conducted to measure the protein levels of cyclin D1, p21, p27, E-cadherin, vimentin, and N-cadherin. The interaction between miR-452-5p and SOX2-OT or HMGB3 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. The mice xenograft model was established to investigate the role of SOX2-OT in vivo.
Results
SOX2-OT and HMGB3 were upregulated, whereas miR-452-5p was downregulated in PCa tissues and cells. Knockdown of SOX2-OT inhibited PCa cell growth and metastasis. MiR-452-5p could directly bind to SOX2-OT and its knockdown reversed the inhibitory effects of SOX2-OT interference on growth and metastasis of PCa cells. HMGB3 was a direct target of miR-452-5p and its knockdown weakened the promotive effects of miR-452-5p silence on growth and metastasis of PCa cells. Moreover, HMGB3 expression was inversely regulated by miR-452-5p and positively modulated by SOX2-OT. Furthermore, SOX2-OT activated the Wnt/β-catenin signaling pathway through increasing HMGB3 expression. Finally, SOX2-OT knockdown hindered tumor growth in vivo by regulating miR-452-5p/HMGB3 axis. Conclusions: SOX2-OT downregulation limited PCa cell growth and metastasis by regulating miR-452-5p/HMGB3 axis and inactivating Wnt/β-catenin signaling pathway, which might offer lncRNA-directed diagnosis and therapy for PCa.