Cancer letters · 2024
TGF-β-induced lncRNA TBUR1 promotes EMT and metastasis in lung adenocarcinoma via hnRNPC-mediated GRB2 mRNA stabilization.
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Huang Lijie, Liu Xiaoxu, Chen Qiuying, Yang Jingyu, Zhang Dongdong, Zhao Yabing, Xu Lele, Li Zhangfu, Liu Xinyuan, Shao Shujuan, Li Dan, Song Yongmei, Liu Xuefeng, Zhan Qimin
Аннотация
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.
Предметные рубрики MeSH
Epithelial-Mesenchymal TransitionHumansRNA, Long NoncodingGRB2 Adaptor ProteinAdenocarcinoma of LungAnimalsLung NeoplasmsMiceTransforming Growth Factor betaMice, NudeGene Expression Regulation, NeoplasticCell MovementCell Line, TumorRNA StabilitySignal TransductionRNA, MessengerA549 CellsMaleFemaleNeoplasm Metastasis