TGF-β诱导的lncRNA TBUR1通过hnRNPC介导的GRB2 mRNA稳定促进肺腺癌的EMT和转移。
TGF-β-induced lncRNA TBUR1 promotes EMT and metastasis in lung adenocarcinoma via hnRNPC-mediated GRB2 mRNA stabilization.
发表日期：2024 Aug 03
作者：
Lijie Huang, Xiaoxu Liu, Qiuying Chen, Jingyu Yang, Dongdong Zhang, Yabing Zhao, Lele Xu, Zhangfu Li, Xinyuan Liu, Shujuan Shao, Dan Li, Yongmei Song, Xuefeng Liu, Qimin Zhan
来源：
CANCER LETTERS
摘要：
转化生长因子-β (TGF-β) 信号通路在诱导上皮间质转化 (EMT) 和促进癌症转移中至关重要。长非编码 RNA (lncRNA) 已成为这些过程中的重要参与者，但其精确机制仍然难以捉摸。在这里，我们证明在肺腺癌细胞 (LUAD) 中，TGF-β 上调的 lncRNA 1 (TBUR1) 被 TGF-β 通过 Smad3/4 信号传导显着激活。功能上，TBUR1触发EMT，增强LUAD细胞体外迁移和侵袭，促进裸鼠转移。从机制上讲，TBUR1 与异质核核糖核蛋白 C (hnRNPC) 相互作用，以 m6A 依赖性方式稳定 GRB2 mRNA。临床上，TBUR1 在 LUAD 组织中表达上调，并与不良预后相关，凸显了其作为 LUAD 预后生物标志物和治疗靶点的潜力。总而言之，我们的研究结果强调了 TBUR1 在介导 TGF-β 诱导的 EMT 和 LUAD 转移中的关键作用，为未来的治疗干预提供了见解。版权所有 © 2024。由 Elsevier B.V. 出版。
The transforming growth factor-β (TGF-β) signaling pathway is pivotal in inducing epithelial-mesenchymal transition (EMT) and promoting cancer metastasis. Long non-coding RNAs (lncRNAs) have emerged as significant players in these processes, yet their precise mechanisms remain elusive. Here, we demonstrate that TGF-β-upregulated lncRNA 1 (TBUR1) is significantly activated by TGF-β via Smad3/4 signaling in lung adenocarcinoma (LUAD) cells. Functionally, TBUR1 triggers EMT, enhances LUAD cell migration and invasion in vitro, and promotes metastasis in nude mice. Mechanistically, TBUR1 interacts with heterogeneous nuclear ribonucleoproteins C (hnRNPC) to stabilize GRB2 mRNA in an m6A-dependent manner. Clinically, TBUR1 is upregulated in LUAD tissues and correlates with poor prognosis, highlighting its potential as a prognostic biomarker and therapeutic target for LUAD. Taken together, our findings underscore the crucial role of TBUR1 in mediating TGF-β-induced EMT and metastasis in LUAD, providing insights for future therapeutic interventions.Copyright © 2024. Published by Elsevier B.V.