RNF31 promotes proliferation and invasion of hepatocellular carcinoma via nuclear factor kappaB activation

RNF31 is a multifunctional RING finger protein implicated in various inflammatory diseases and cancers. It functions as a core component of the linear ubiquitin chain assembly complex (LUBAC), which activates the nuclear factor kappaB (NF-κB) pathway via the generation of the Met1-linked linear ubiq...

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Published in:Scientific reports 2024-01, Vol.14 (1), p.346-346, Article 346
Main Authors: Hoshino, Kouki, Nakazawa, Seshiru, Yokobori, Takehiko, Hagiwara, Kei, Ishii, Norihiro, Tsukagoshi, Mariko, Igarashi, Takamichi, Araki, Kenichiro, Harimoto, Norifumi, Tokunaga, Fuminori, Shirabe, Ken
Format: Article
Language:English
Subjects:
631/67/1504/1610/4029
692/4020/1503/1607/1610/4029
Carcinoma, Hepatocellular - pathology
Cell growth
Cell Proliferation
Hepatocellular carcinoma
Humanities and Social Sciences
Humans
Immunohistochemistry
Inflammatory diseases
Liver cancer
Liver Neoplasms - pathology
mRNA
multidisciplinary
Neoplastic Processes
NF-kappa B - metabolism
NF-κB protein
RING finger proteins
Science
Science (multidisciplinary)
Survival
Therapeutic targets
Tumor necrosis factor-TNF
Ubiquitin - metabolism
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
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Summary:RNF31 is a multifunctional RING finger protein implicated in various inflammatory diseases and cancers. It functions as a core component of the linear ubiquitin chain assembly complex (LUBAC), which activates the nuclear factor kappaB (NF-κB) pathway via the generation of the Met1-linked linear ubiquitin chain. We aimed to clarify the role of RNF31 in the pathogenesis of hepatocellular carcinoma (HCC) and its relevance as a therapeutic target. High RNF31 expression in HCC, assessed by both immunohistochemistry and mRNA levels, was related to worse survival rates among patients with HCC. In vitro experiments showed that RNF31 knockdown in HCC cell lines led to decreased cell proliferation and invasion, as well as suppression of tumor necrosis factor (TNF)-α-induced NF-κB activation. Treatment with HOIPIN-8, a specific LUBAC inhibitor that suppresses RNF31 ubiquitin ligase (E3) activity, showed similar effects, resulting in decreased cell proliferation and invasion. Our clinical and in vitro data showed that RNF31 is a prognostic factor for HCC that promotes tumor aggressiveness via NF-κB activation.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-50594-3