Individual and combined effects of DNA methylation and copy number alterations on miRNA expression in breast tumors.

摘要: The global effect of copy number and epigenetic alterations on miRNA expression in cancer is poorly understood. In the present study, we integrate genome-wide DNA methylation, identify genetic mechanisms underlying dysregulation breast cancer. We 70 miRNAs whose was associated with or both. Among these, five families are represented. Interestingly, members these encoded different chromosomes complementarily altered by gain hypomethylation across patients. an independent cohort 123 patients, 41 were confirmed respect to aberration pattern association expression. vitro functional experiments performed cell lines mimics evaluate phenotype replicated miRNAs. let-7e-3p, which tumors found hypermethylation, shown induce apoptosis reduce viability, low let-7e-3p poorer prognosis. overexpression three other gain, miR-21-3p, miR-148b-3p miR-151a-5p, increases proliferation lines. addition, miR-151a-5p enhances levels phosphorylated AKT protein. Our data provide novel evidence behind study contributes understanding how methylation influence expression, emphasizing functionality through redundant encoding, suggests important