Heterochromatin protein HP1{gamma} promotes colorectal cancer progression and is regulated by miR-30a

Colorectal cancer (CRC) pathogenesis remains incompletely understood. Here we report that the heterochromatin protein HP1γ is upregulated commonly in human CRC where it promotes cell proliferation in vitro and in vivo. Gene expression and promoter binding experiments demonstrated that HP1γ directly regulated CDKN1A (p21Waf1/Cip1) in a manner associated with methylation of histone H3K9 on its promoter. We identified miR-30 as a tumor suppressive microRNA that targets HP1γ in vitro and in vivo to specifically suppress the growth of colorectal cancer in mouse xenograft models. MiR-30a was widely downregulated in primary human CRC tissues where its expression correlated inversely with high levels of HP1γ protein. Our results identify a new miR-30a/HP1γ/p21 regulatory axis controlling CRC development which may offer prognostic and therapeutic opportunities.