miR-203, a tumor suppressor frequently down-regulated by promoter hypermethylation in rhabdomyosarcoma.
Yarui Diao, Xing Guo, Lei Jiang, Gang Wang, Chao Zhang, Jun Wan, Yan Jin, Zhenguo Wu
Index: J. Biol. Chem. 289(1) , 529-39, (2014)
Full Text: HTML
Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma found in children and young adults. It is characterized by the expression of a number of skeletal muscle-specific proteins, including MyoD and muscle α-actin. However, unlike normal myoblasts, RMS cells differentiate poorly both in vivo and in culture. As microRNAs are known to regulate tumorigenesis, intensive efforts have been made to identify microRNAs that are involved in RMS development. In this work, we found that miR-203 was frequently down-regulated by promoter hypermethylation in both RMS cell lines and RMS biopsies and could be reactivated by DNA-demethylating agents. Re-expression of miR-203 in RMS cells inhibited their migration and proliferation and promoted terminal myogenic differentiation. Mechanistically, miR-203 exerts its tumor-suppressive effect by directly targeting p63 and leukemia inhibitory factor receptor in RMS cells, which promotes myogenic differentiation by inhibiting the Notch and the JAK1/STAT1/STAT3 pathways, respectively. Our work reveals that miR-203 functions as a tumor suppressor in RMS development.
Related Compounds
Related Articles:
2012-05-18
[J. Biol. Chem. 287(21) , 17318-30, (2012)]
Impaired post-translational folding of familial ALS-linked Cu, Zn superoxide dismutase mutants.
2007-02-07
[EMBO J. 26(3) , 855-66, (2007)]
Neogenesis of pancreatic endocrine cells in copper-deprived rat models.
2000-07-01
[Pancreas 21(1) , 63-8, (2000)]
Schumacher's guide for: Bisulfite conversion of DNA for methylation fine-mapping. Schumacher A.
[Schumacher's Guide , (2009) 1 , 1-6]
F430 Model Chemistry. A Reexamination of the [1, 4, 7, 10, 13-Pentaazacyclohexadecane-14, 16-dionato (2-)] nickel (II)-Induced Formation of Methane from Methyl Coenzyme-M. Zhang Z, et al.
[Inorganic Chemistry 35(16) , 4649-4655, (1966)]