TGF-β-induced lncRNA TBUR1 promotes EMT and metastasis in lung adenocarcinoma via hnRNPC-mediated GRB2 mRNA stabilization

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

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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

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.

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