2. Academic Validation
  3. TGF-β-induced lncRNA TBUR1 promotes EMT and metastasis in lung adenocarcinoma via hnRNPC-mediated GRB2 mRNA stabilization

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

  • Cancer Lett. 2024 Sep 28:600:217153. doi: 10.1016/j.canlet.2024.217153.
Lijie Huang 1,  Xiaoxu Liu 2,  Qiuying Chen 2,  Jingyu Yang 2,  Dongdong Zhang 3,  Yabing Zhao 4,  Lele Xu 2,  Zhangfu Li 5,  Xinyuan Liu 4,  Shujuan Shao 4,  Dan Li 5,  Yongmei Song 5,  Xuefeng Liu 6,  Qimin Zhan 7
Affiliations

Affiliations

  • 1 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.
  • 2 Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
  • 3 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; Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 4 Liaoning Key Laboratory of Proteomics, Dalian Medical University, Dalian 116044, China.
  • 5 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.
  • 6 Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China. Electronic address: ixuee@sina.com.
  • 7 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; Soochow University Cancer Institute, Suzhou 215000, China; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: zhanqimin@bjmu.edu.cn.
PMID: 39102940 DOI: 10.1016/j.canlet.2024.217153
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.

Keywords

GRB2; LUAD; hnRNPC; lncRNA.

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