长链非编码 RNA ELF3-AS1 通过与 Krüppel 样因子 8 相互作用促进膀胱癌进展。
The lncRNA ELF3-AS1 promotes bladder cancer progression by interaction with Krüppel-like factor 8.
机构信息
Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou City, Fujian Province, 362000, China.
Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou City, Fujian Province, 362000, China.
出版信息
Biochem Biophys Res Commun. 2019 Jan 15;508(3):762-768. doi: 10.1016/j.bbrc.2018.11.183. Epub 2018 Dec 7.
Accumulating evidence has shown the critical role of long non-coding RNAs (lncRNAs) during cancer progression. However, the involvement of ELF3-AS1 in bladder cancer (BC) remains largely unclear. By lncRNA profiling, we identified ELF3-AS1 as a novel oncogenic lncRNA during bladder cancer development. ELF3-AS1 was highly expressed in bladder cancer and correlated with poor prognosis. ELF3-AS1 could increase viability and migration of bladder cancer cells in vitro and promoted xenograft tumor growth in vivo. Furthermore, ELF3-AS1 could interact with KLF8 to stabilize KLF8 by protecting it from proteasome-mediated degradation. KLF8 in turn could bind ELF3-AS1 promoter and transactivate ELF3-AS1 expression. The positive feedback loop between ELF3-AS1 and KLF8 enhanced KLF8 signaling by increasing MMP9 expression. Collectively, our study has unraveled a novel mechanism of ELF3-AS1-mediated oncogenesis in bladder cancer by reinforcement of ELF3-AS1/KLF8 signaling with potential implications for therapeutic intervention.
越来越多的证据表明，长非编码 RNA（lncRNA）在癌症进展过程中起着关键作用。然而，ELF3-AS1 在膀胱癌（BC）中的作用在很大程度上仍不清楚。通过 lncRNA 谱分析，我们发现 ELF3-AS1 是膀胱癌发展过程中的一种新型致癌 lncRNA。ELF3-AS1 在膀胱癌中高表达，并与预后不良相关。ELF3-AS1 可增加膀胱癌细胞在体外的活力和迁移能力，并促进体内异种移植肿瘤的生长。此外，ELF3-AS1 可以与 KLF8 相互作用，通过保护 KLF8 免受蛋白酶体介导的降解来稳定 KLF8。反过来，KLF8 可以结合 ELF3-AS1 启动子并反式激活 ELF3-AS1 的表达。ELF3-AS1 和 KLF8 之间的正反馈环通过增加 MMP9 的表达增强了 KLF8 信号。综上所述，我们的研究揭示了 ELF3-AS1 在膀胱癌中介导致癌作用的新机制，通过 ELF3-AS1/KLF8 信号的增强，为治疗干预提供了潜在的意义。
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