Xiao Mengqing, Liu Jianye, Xiang Liang, Zhao Kai, He Dong, Zeng Qinghai, Zhang Qun, Xie Dan, Deng Minhua, Zhu Yuxing, Zhang Yeyu, Liu Yan, Bo Hao, Liu Xiaoming, Chen Xingyu, Gong Lian, Bao Ying, Hu Yi, Cheng Yaxin, Deng Liping, Zhu Rongrong, Xing Xiaowei, Zhou Ming, Xiong Wei, Zhou Yanhong, Zhou Jianda, Li Xiaohui, Cao Ke
Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, China.
Department of Urology, Third Xiangya Hospital of Central South University, Changsha, China.
Clin Transl Med. 2020 Dec;10(8):e241. doi: 10.1002/ctm2.241.
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.
长链非编码RNA（lncRNAs）在膀胱尿路上皮癌（BUC）进展中起关键作用。然而，这一作用背后的分子机制尚未阐明。在此，我们发现lncRNA MAFG-AS1在BUC中高表达，且与BUC的侵袭性特征和不良预后相关。我们证明MAFG-AS1在体外和体内均可促进BUC的增殖、侵袭、转移及上皮-间质转化。机制上，MAFG-AS1与Hu抗原R（HuR）直接结合可募集泛素特异性蛋白酶5（USP5），防止HuR通过泛素化降解。我们进一步证明，MAFG-AS1的过表达可通过促进结合的HuR介导的多聚嘧啶序列结合蛋白1（PTBP1）的稳定性来上调其表达。总之，这些发现表明MAFG-AS1通过调节HUR/PTBP1轴促进BUC进展。靶向MAFG-AS1可能为BUC的个体化治疗提供新策略，并为其预后提供潜在生物标志物。
