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

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Tumor Biology

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.

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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).

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    Authors and Affiliations

    1. Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, China

      Wen-Jie Wu, Jia Shi & Zhi-Xiang Wu

    2. Key Laboratory of Kidney Disease Pathogenesis and Intervention of Hubei Province, College of Medicine, Hubei Polytechnic University, Huangshi, Hubei, 435003, China

      Gang Hu, Xin Yu & Bin Liu

    3. Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), 197, Rui Jin Er Road, Shanghai, 200025, China

      Han Lu

    4. Department of Anesthesiology, Jianli Second People’s Hospital, Jianli, Hubei, 433325, China

      Ming-Liang Yang

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    1. Wen-Jie Wu
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    3. Gang Hu
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    Correspondence to Bin Liu or Zhi-Xiang Wu.

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    Wen-Jie Wu and Jia Shi contributed equally to this work.

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    Wu, WJ., Shi, J., Hu, G. et al. Wnt/β-catenin signaling inhibits FBXW7 expression by upregulation of microRNA-770 in hepatocellular carcinoma. Tumor Biol. 37, 6045–6051 (2016). https://doi.org/10.1007/s13277-015-4452-5

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    • DOI: https://doi.org/10.1007/s13277-015-4452-5

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