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Title: The E3 ubiquitin ligase RNF146 promotes colorectal cancer by activating the Wnt/β-catenin pathway via ubiquitination of Axin1

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [2];  [1]
  1. Department of Anus Bowel, Xianyang Central Hospital, No. 78 People East Road, Xianyang, Shaanxi, 712000 (China)
  2. Department of Anus Bowel, The First People's Hospital of Xianyang, No. 10 Biyuan Road, Xianyang, Shaanxi, 712000 (China)

Highlights: • RNF146 is increased and correlated with poor prognosis in colorectal cancer. • RNF146 exerts oncogenic role in colorectal cancer. • RNF146 activates the Wnt/β-catenin signaling via ubiquitination of Axin1. The E3 ubiquitin ligase ring finger protein 146 (RNF146) has been implicated in tumor development. However, the role and clinical significance of RNF146 in colorectal cancer (CRC) remain unknown. In this study, we reported for the first time that RNF146 was upregulated in CRC tissues as well as in cell lines. Further, RNF146 expression was independent prognostic factor for poor outcome of CRC patients. RNF146 knockdown in cell lines inhibited cell growth, promoted cell apoptosis in vitro and suppressed colorectal tumor growth in vivo. Mechanistic investigations revealed that RNF146 exerted oncogenic role through ubiquitination of Axin1 to activate β-catenin signaling. In addition, RNF146 expression was positively correlated with β-catenin expression in CRC tissues. Collectively, our data suggest that RNF146 might function as a oncogene in human CRC, and represent a promising prognostic factor and a valuable therapeutic target for CRC.

OSTI ID:
23105638
Journal Information:
Biochemical and Biophysical Research Communications, Vol. 503, Issue 2; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
Country of Publication:
United States
Language:
English