MYEOV functions as an amplified competing endogenous RNA in promoting metastasis by activating TGF-β pathway in NSCLC.
Lishan FangShanshan WuXun ZhuJunchao CaiJueheng WuZhenjian HeLei LiuMusheng ZengErwei SongJun LiMeng-Feng LiHongyu GuanPublished in: Oncogene (2018)
Non-small cell lung cancer (NSCLC) remains a major cause of death worldwide. As metastatic disease is primarily responsible for the poor clinical outcome of NSCLC, it is important to understand the process, and its underlying molecular mechanism as well, via which NSCLC cells disseminate. In this study, we identified a new competing endogenous RNA (ceRNA), namely, the MYEOV transcript, and found that it is upregulated in NSCLC and associated with a poor prognosis of the disease. We further uncovered that the MYEOV ceRNA plays a critical role in the invasion and metastasis of NSCLC cells. Intriguingly, the MYEOV ceRNA exerted its pro-metastatic function independent of its protein-coding capacity, but in a miR-30c-2-3p binding-dependent manner. Further experiments demonstrated that the MYEOV ceRNA sequestered miR-30c-2-3p from binding its targets TGFBR2 and USP15 mRNAs, which in turn leading to constitutive activation of TGF-β signaling and tumor progression in NSCLC. By identifying a new layer of regulatory modality for TGF-β signaling, our findings extend the current understanding on the molecular mechanism mediating NSCLC progression and highlight a potential role of MYEOV transcript to serve as the therapeutic target.
Keyphrases
- small cell lung cancer
- long non coding rna
- poor prognosis
- advanced non small cell lung cancer
- brain metastases
- induced apoptosis
- cell proliferation
- squamous cell carcinoma
- epidermal growth factor receptor
- signaling pathway
- cell cycle arrest
- long noncoding rna
- rna seq
- oxidative stress
- transcription factor
- binding protein
- risk assessment
- epithelial mesenchymal transition
- single cell
- sensitive detection
- single molecule
- amino acid