PGAM1, regulated by miR-3614-5p, functions as an oncogene by activating transforming growth factor-β (TGF-β) signaling in the progression of non-small cell lung carcinoma
| Autor: | Jiuling Cheng, Shanshan Chen, Ping Li, Hao Yang, Fangfang Li, Guojun Zhang, Guangying Cui, Tiandong Kong, Lu Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cancer Research Lung Neoplasms Gene Expression medicine.disease_cause 0302 clinical medicine Cell Movement Transforming Growth Factor beta Carcinoma Non-Small-Cell Lung Phosphoglycerate Mutase lcsh:Cytology Middle Aged Cell invasion Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Transforming Growth Factors Disease Progression Female Signal transduction Signal Transduction Adult China Epithelial-Mesenchymal Transition Immunology Biology Article 03 medical and health sciences Cellular and Molecular Neuroscience In vivo medicine Gene silencing Humans Neoplasm Invasiveness lcsh:QH573-671 Lung cancer Aged Cell Proliferation Oncogene Cell Biology Oncogenes medicine.disease respiratory tract diseases MicroRNAs 030104 developmental biology Anaerobic glycolysis Cancer research Carcinogenesis Non-small-cell lung cancer Transforming growth factor |
| Zdroj: | Cell Death and Disease, Vol 11, Iss 8, Pp 1-16 (2020) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Phosphoglycerate mutase 1 (PGAM1) is a recently identified key catalytic enzyme in aerobic glycolysis. Recent literature has documented that dysregulated PGAM1 expression is associated with tumorigenesis in various cancers. However, the expression status and biological function of PGAM1 in non-small-cell lung cancer (NSCLC) are poorly elucidated. In this study, we found that PGAM1 was overexpressed in NSCLC tissues and that high expression of PGAM1 was associated with poor prognosis in NSCLC patients. Functionally, gain- and loss-of-function analysis showed that PGAM1 promoted proliferation and invasion in vitro, and facilitated tumor growth in vivo. Mechanistically, the transforming growth factor-β (TGF-β) signaling pathway was also markedly impaired in response to PGAM1 silencing. Additionally, we verified that PGAM1 was inhibited by miR-3614-5p via direct targeting of its 3’-untranslated regions in a hypoxia-independent manner. Furthermore, overexpression of miR-3614-5p attenuated NSCLC cell proliferation and invasion, and these effects could be partially reversed by reintroduction of PGAM1. Conclusively, our results suggest that the miR-3614-5p/PGAM1 axis plays a critical role during the progression of NSCLC, and these findings may provide a potential target for the development of therapeutic strategies for NSCLC patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|