Tumor Biology

, Volume 37, Issue 5, pp 6045–6051 | Cite as

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

Original Article

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.

Keywords

Hepatocellular carcinoma (HCC) FBXW7 MicroRNA-770 Wnt/β catenin 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation, People’s Republic of China, Grant No. 31401185 (to Dr. Bin Liu) and No. 81402478 (to Dr. Zhi-Xiang Wu).

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Pediatric SurgeryXin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Key Laboratory of Kidney Disease Pathogenesis and Intervention of Hubei Province, College of MedicineHubei Polytechnic UniversityHuangshiChina
  3. 3.Department of Anesthesiology, Ruijin HospitalShanghai Jiao-Tong University School of Medicine (SJTU-SM)ShanghaiChina
  4. 4.Department of AnesthesiologyJianli Second People’s HospitalJianliChina

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