[摘要]：Constitutive NF-kappa B activation has causative roles in adult T cell leukemia (ATL) caused by HTLV-1 and other cancers. Here, we report a pathway involving Polycomb-mediated miRNA silencing and NF-kappa B activation. We determine the miRNA signatures and reveal miR-31 loss in primary ATL cells. MiR-31 negatively regulates the noncanonical NF-kappa B pathway by targeting NF-kappa B inducing kinase (NIK). Loss of miR-31 therefore triggers oncogenic signaling. In ATL cells, miR-31 level is epigenetically regulated, and aberrant upregulation of Polycomb proteins contribute to miR-31 downregulation in an epigenetic fashion, leading to activation of NF-kappa B and apoptosis resistance. Furthermore, this emerging circuit operates in other cancers and receptor-initiated NF-kappa B cascade. Our findings provide a perspective involving the epigenetic program, inflammatory responses, and oncogenic signaling.
