Heterochromatin Protein HP1γ Promotes Colorectal Cancer Progression and Is Regulated by miR-30a

Colorectal cancer pathogenesis remains incompletely understood. Here, we report that the heterochromatin protein HP1 gamma is upregulated commonly in human colorectal cancer, where it promotes cell proliferation in vitro and in vivo. Gene-expression and promoter-binding experiments demonstrated that HP1 gamma directly regulated CDKN1A (p21(Waf1/Cip1)) in a manner associated with methylation of histone H3K9 on its promoter. We identified miR-30a as a tumor-suppressive microRNA that targets HP1 gamma 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 colorectal cancer tissues, where its expression correlated inversely with high levels of HP1 gamma protein. Our results identify a new miR-30a/HP1 gamma/p21 regulatory axis controlling colorectal cancer development, which may offer prognostic and therapeutic opportunities. (C) 2015 AACR.