Wnt/β-catenin signaling inhibits FBXW7 expression by upregulation of microRNA-770 in hepatocellular carcinoma.

Abstract

FBXW7 (F-box and WD repeat domain-containing 7) is the F-box protein component of a Skp1-Cul1-F-box protein-type (SCF-type) ubiquitin ligase. Previous studies have shown that FBXW7 serves as a tumor suppressor and is frequently downregulated in many types of human neoplasms. However, the molecular mechanisms for its downregulation remain poorly understood. Hyperactivation of Wnt/β-catenin signaling pathway is viewed as crucial for tumorigenesis, including hepatocellular carcinoma (HCC). In the present study, we show that protein levels, but not message RNA, of FBXW7 were suppressed by Wnt3a treatment or transfection of a constitutively activated β-catenin in HCC cells. Besides, microRNA-770 was identified as an important downstream target of Wnt/β-catenin signaling, to inhibit FBXW7 expression through targeting its 3'-untranslated region. Thus, our results suggest a previously unknown Wnt/β catenin-miR-770-FBXW7 molecular network in the HCC development.