State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China.
Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
Cancer Lett. 2024 Sep 28;600:217153. doi: 10.1016/j.canlet.2024.217153. Epub 2024 Aug 3.
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 ribonucleoprotein C (hnRNPC) to stabilize GRB2 mRNA in an mA-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.
转化生长因子-β（TGF-β）信号通路在诱导上皮-间充质转化（EMT）和促进癌症转移中起着关键作用。长非编码 RNA（lncRNA）已成为这些过程中的重要参与者，但它们的确切机制仍不清楚。在这里，我们证明 TGF-β 通过 Smad3/4 信号在肺腺癌（LUAD）细胞中显著激活 TGF-β 上调的 lncRNA 1（TBUR1）。在功能上，TBUR1 触发 EMT，增强 LUAD 细胞在体外的迁移和侵袭，并促进裸鼠的转移。在机制上，TBUR1 与异质核核糖核蛋白 C（hnRNPC）相互作用，以 mA 依赖性方式稳定 GRB2 mRNA。临床上，TBUR1 在 LUAD 组织中上调，并与预后不良相关，这突出了其作为 LUAD 预后生物标志物和治疗靶点的潜力。总之，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新的见解。
