Abstract:
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 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.
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。长链非编码RNA(lncRNAs)已经成为这些过程中的重要参与者,然而,他们的精确机制仍然难以捉摸。这里,我们证明TGF-β上调的lncRNA1(TBUR1)在肺腺癌(LUAD)细胞中通过Smad3/4信号传导被TGF-β显着激活。功能上,TBUR1触发EMT,在体外增强LUAD细胞的迁移和侵袭,并促进裸鼠的转移。机械上,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GRB2mRNA。临床上,TBUR1在LUAD组织中上调,并与不良预后相关。强调其作为LUAD预后生物标志物和治疗靶点的潜力。一起来看,我们的发现强调了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见解。