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ARTICLE

RNF145 Promotes Hepatocellular Carcinoma Metastasis through Ubiquitination and Degradation of PCDH9

Huan Zhang1,#, Zhangwendi Xu1,#, Yien Xu1,#, Mao Li2, Lingrui Liu1, Caiyun He1,, Wenhuan Zhong1,, Jiliang Qiu1,*
1 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
2 School of Medicine, Jishou University, Jishou, 416000, China
* Corresponding Authors: Caiyun He. Email: hecy@sysucc.org.cn; Wenhuan Zhong. Email: zhongwh@sysucc.org.cn; Jiliang Qiu. Email: qiujl@sysucc.org.cn
# These authors contributed equally to this work and share first authorship

Oncology Research https://doi.org/10.32604/or.2025.073079

Received 10 September 2025; Accepted 07 November 2025; Published online 21 November 2025

Abstract

Objective: Ring finger protein 145 (RNF145), an E3 ubiquitin ligase, is significantly upregulated in hepatocellular carcinoma (HCC). However, its role in HCC remains unknown. The study aimed to investigate the functions and underlying mechanisms of RNF145 in HCC. Methods: The role of RNF145 in HCC was investigated using data from The Cancer Genome Atlas (TCGA) and in vitro experimental assays. Its oncogenic functions were assessed using the transwell migration assay and the wound-healing assay. The molecular mechanism was explored through protein immunoprecipitation and western blot analyses. Data from public databases were analyzed to correlate RNF145 expression with clinicopathological features. Univariate and multivariate Cox analyses established RNF145 as an independent prognostic factor. Subsequently, a prognostic nomogram was constructed. Results: RNF145 was upregulated in HCC. The expression level of RNF145 in HCC showed significant correlations with histological grade, pathological stage, and vascular invasion. Functionally, knockdown of RNF145 effectively abolished the migratory and invasive capacities of HCC cells. This pro-metastatic effect is mediated through the RNF145-driven ubiquitination and subsequent degradation of protocadherin 9 (PCDH9). Conclusion: Our findings confirm the significant upregulation of RNF145 in HCC and promote metastasis by facilitating PCDH9 ubiquitination and degradation, highlighting its role as a prognostic biomarker and a potential therapeutic target.

Keywords

Ring finger protein 145 (RNF145); protocadherin 9 (PCDH9); hepatocellular carcinoma; metastasis

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