Long noncoding RNAs (lncRNAs) play a crucial role in progression of bladder urothelial carcinoma (BUC). However, the molecular mechanisms behind this role have not been elucidated yet. Here, we found that the lncRNA MAFG-AS1, which is highly expressed in BUC, is correlated with aggressive characteristics and poor prognosis of BUC. We demonstrate that MAFG-AS1 can promote BUC proliferation, invasion, metastasis, and epithelial-mesenchymal transition in vitro and in vivo. Mechanistically, MAFG-AS1 direct binding to Hu antigen R (HuR) could recruit ubiquitin-specific proteinase 5 (USP5) to prevent HuR from degrading by ubiquitination. We further demonstrate that overexpression of MAFG-AS1 can upregulate the expression of polypyrimidine tract-binding protein 1 (PTBP1) through promoting its stability mediated by bound HuR. In conclusion, these findings indicate that MAFG-AS1 promotes the progression of BUC via regulation of the HUR/PTBP1 axis. Targeting MAFG-AS1 may provide a novel strategy for individualized therapy and a potential biomarker for prognosis of BUC.
Keywords: HuR; MAFG-AS1; PTBP1; bladder urothelial carcinoma.
© 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.