2. Academic Validation
  3. RNF180 suppressed aggressiveness by degrading NOTCH1, TRIM24 and FOXC1, and chemoresistance by degrading ACC1 and ACLY in colorectal cancer

RNF180 suppressed aggressiveness by degrading NOTCH1, TRIM24 and FOXC1, and chemoresistance by degrading ACC1 and ACLY in colorectal cancer

  • Int Immunopharmacol. 2025 Sep 6:165:115445. doi: 10.1016/j.intimp.2025.115445.
Ning Li 1,  Rui Zhang 2,  Xiang-Xuan Zhao 3,  Lei Zhou 1,  Ya-Lei Li 4,  Zheng-Guo Cui 5,  Hua-Chuan Zheng 6
Affiliations

Affiliations

  • 1 Cancer Center and Center of Translational Medicine, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
  • 2 Department of Colorectal Surgery, Liaoning Cancer Hospital, Shenyang 110042, China.
  • 3 Center for Innovative Engineering Technology in Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China.
  • 4 Department of Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, China.
  • 5 Department of Environmental Health, University of Fukui School of Medical Sciences, Fukui 910-1193, Japan.
  • 6 Cancer Center and Center of Translational Medicine, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China. Electronic address: zheng_huachuan@hotmail.com.
PMID: 40915184 DOI: 10.1016/j.intimp.2025.115445
Abstract

Ring finger protein 180 (RNF180) is an E3 ubiquitin-protein Ligase that promotes polyubiquitination and degradation. We analyzed the roles and molecular mechanisms of RNF180 during the tumorigenesis and progression of colorectal Cancer (CRC) through bioinformatics analysis, in vivo and vitro experiments. RNF180 overexpression was observed in CRC, and positively associated with T, N and TNM staging or differentiation. RNF180 inhibited proliferation, promoted Apoptosis, and inhibited migration and invasion of CRC cells by interacting with and degrading NOTCH1, TRIM24 and FOXC1 via their ubiquitination and proteasomal degradation, and by inactivating Akt pathway. RNF180 might suppress the chemoresistance by mitigating lipid droplet assembly and ACC1- and ACLY- mediated lipogenesis in CRC cells via their ubiquitination and proteasomal degradation of ACC1 and ACLY. Its knockout might enhance the sensitivity of chemically-induced colorectal carcinogenesis in Lgr5-cre/RNF180 f/f mice. RNF180-correlated genes were involved in neuroactive ligand-receptor interaction, glycosaminoglycan binding, ECM structural constituents and organization, receptor ligand activity, cell adhesion, mRNA splicing and so forth in CRC. The expression of RNF180 may be used as a biomarker for the diagnosis, as a prognostic indicator, and as a gene therapy target of CRC.

Keywords

Aggressiveness; Chemoresistance; Colorectal cancer; Lipid droplet formation; RNF180.

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