Comprehensive silencing of target-sharing microRNAs is a mechanism for SIRT1 overexpression in cancer

However, the molecular basis of how SIRT1 is elevated in cancer is less understood. Here we show that cancer-related SIRT1 overexpression is due to evasion of Sirt1 mRNA from repression by a group of Sirt1 -targeting microRNAs (miRNAs) that might be robustly silenced in cancer.

Our comprehensive library-based screening and subsequent miRNA gene profiling revealed a housekeeping gene-like broad expression pattern and strong CpG island-association of the Sirt1 -targeting miRNA genes. This suggests aberrant CpG DNA methylation as the mechanistic background for malignant SIRT1 elevation. Our work also provides an example where epigenetic mechanisms cause the group-wide regulation of miRNAs sharing a common key target.