Semaphorin 5A drives melanoma progression: role of Bcl-2, miR-204 and c-Myb.

摘要: Melanoma, the most aggressive form of skin cancer, is characterized by high rates metastasis, drug resistance and mortality. Here we investigated role Semaphorin 5A (Sema5A) on properties associated with melanoma progression factors involved in Sema5A regulation. Western blotting, qRT-PCR, Chromatin immunoprecipitation (ChIP) assay, immunohistochemistry patient specimens xenograft tissues, vitro Transwell assay for cell migration invasion evaluation, capillary-like structure formation analysis. A significant correlation mRNA expression was observed analyzing GEO profile dataset. Endogenous protein detected 95% human lines tested, 70% metastatic from patients affected melanoma, 16% situ melanoma showed a focal positivity. We demonstrated that regulates vasculogenic structures. also found an increase at both level after forced Bcl-2. By use transcriptional proteasome inhibitors, Bcl-2 increases stability protein. Moreover, ChIP under control transcription factor c-Myb recruitment promoter increased overexpression. Finally, concomitant decrease Sema5A, proteins cells miR-204 Overall our data provide evidences supporting involvement Bcl-2, regulating its expression.