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Epigenetic profiling identifies MIR10A-5 p as a putative tumor suppresor in Ewing sarcoma and rhabdomyosarcoma
Introduction: Aberrant DNA methylation is thought to be closely related to the development of cancer. Therefore, the identification of specific DNA methylation markers in Ewing sarcoma (ES) and Rhabdomyosarcoma (RMS) would be helpful for understanding the pathogenetic mechanism as well as for developing new therapies. We analyzed the methylome of ES and RMS tumors and cell lines.
Methods: Infinium 450k Illumina methylation array. Western blot, qRT-PCR, clonogenic, proliferation and migration assays. iTRAQ proteomic profile.
Results: ES and RMS showed hypermethylation in MIR10A-5 p promoter, thus suggesting an inhibition of its expression. MIR10A-5 p has been related to several cancers and linked to development. MIR10A-5 p is low expressed in ES and RMS cell lines and patient samples and 5'-aza treatment restored its expression. MIR10A-5 p stable overexpression in 2 ES (A673, TC252) and 3 RMS (Rh4, Rh30, RMS13) cell lines reduced proliferation, inhibited clonogenic growth and decreased cellular migration. Proteomic profile of A673 MIR10A-5 p model identified CRKL, V-Crk Avian Sarcoma Virus CT10 Oncogene Homolog-Like, as one of the protein down-regulated due to MIR10A-5 p reintroduction. Further characterization of the role of CRKL and MIR10A-5 p tumor suppressor activities in ES and RMS is on-going.
Conclusion: Our results uncover MIR10A-5 p as a putative tumor suppressor in ES and RMS.