2. Academic Validation
  3. SIAH1/CTR9 axis promotes the epithelial-mesenchymal transition of hepatocellular carcinoma

SIAH1/CTR9 axis promotes the epithelial-mesenchymal transition of hepatocellular carcinoma

  • Carcinogenesis. 2023 Apr 11;bgad021. doi: 10.1093/carcin/bgad021.
Zhiyi Liu 1 2 3,  Pengchao Luo 1 2 3,  Kuan Cao 1 2 3,  Qinghe Hu 1 2 3,  Bin Hu 1 2 3,  Licheng Cui 1 2 3,  Xiaotian Wang 1 2 3,  Hengliang Shi 1 2 3 4,  Bin Zhang 1 2 3,  Renhao Wang 1 2 3
Affiliations

Affiliations

  • 1 Research Center of Digestive Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 2 Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 3 Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 4 Central Laboratory, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
PMID: 37038329 DOI: 10.1093/carcin/bgad021
Abstract

SIAH1 has been reported to participate in several human cancers, including HCC. However, the effect of SIAH1 on the EMT has not been reported in HCC cells. Here, we discovered the inhibitory effect of SIAH1 on HCC cell migration and invasion, which was related with regulating EMT. Molecularly, a yeast two-hybrid experiment indicated that CTR9 was a potential interacting protein of SIAH1, which was further verified by co-immunoprecipitation (co-IP) assays. Furthermore, SIAH1 inhibited the EMT of HCC cells through negatively regulating CTR9. Importantly, CTR9 was ubiquitinated and degraded by SIAH1 via the Proteasome pathway in HCC cells. Additionally, it was showed that SIAH1 mainly mediated the K48-linked polyubiquitination on CTR9. Finally, the protein level of CTR9 was found to be inversely correlated with SIAH1 in human HCC tissues. Summed up all together, these findings reveal that SIAH1/CTR9 axis promotes the EMT of HCC cells and is a promising therapeutic target for HCC therapy.

Keywords

CTR9; HCC; SIAH1; migration; ubiquitination.

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