1. TGF-? regulates the ERK/MAPK pathway independent of the SMAD pathway by repressing miRNA-124 to increase MALAT1 expression in nasopharyngeal carcinoma.
- Author
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Du M, Chen W, Zhang W, Tian XK, Wang T, Wu J, Gu J, Zhang N, Lu ZW, Qian LX, Fei Q, Wang Y, Peng F, He X, and Yin L
- Subjects
- Carcinoma genetics, Cell Line, Tumor, Cell Movement genetics, Cell Proliferation genetics, Gene Expression Regulation, Neoplastic, Humans, MAP Kinase Signaling System genetics, Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms genetics, Signal Transduction genetics, Smad2 Protein metabolism, Smad3 Protein metabolism, Smad4 Protein metabolism, Carcinoma pathology, MicroRNAs genetics, Nasopharyngeal Neoplasms pathology, RNA, Long Noncoding genetics, Transforming Growth Factor beta metabolism
- Abstract
Transforming growth factor beta (TGF-?), a pleiotropic cytokine, promotes cell proliferation and migration in multiple cancers, including nasopharyngeal carcinoma (NPC). microRNA-124 (miR-124) becomes downregulated in NPC and inhibits the tumorigenesis of this disease. However, the role of miR-124 in TGF-?-induced NPC development remains unknown. In this study, constant TGF-? stimulation repressed miR-124 expression, whereas miR-124 overexpression antagonized TGF-?-promoted NPC cell growth and migration. miR-124 overexpression decreased p-SMAD2/3, SMAD4, and p-ERK levels, indicating that ectopic miR-124 overexpression inhibited SMAD and non-SMAD pathways. Pro-oncogenic lncRNA MALAT1 was targeted by miR-124 that regulated ERK/MAPK by targeting MALAT1 independent of the SMAD signaling pathway. In conclusion, our work clarified the significant role of miR-124 in TGF-? signaling pathways independent of the SMAD signaling pathway and showed the potential of miR-124 as a new therapeutic target against NPC., (Copyright © 2018. Published by Elsevier Masson SAS.)
- Published
- 2018
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