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TRIM55 Promotes Proliferation of Hepatocellular Carcinoma Through Stabilizing TRIP6 to Activate Wnt/β-Catenin Signaling
PURPOSE: Tripartite motif containing 55 (TRIM55) is a member of the TRIM family and functions as an E3 ubiquitin ligase. It acts as a cancer promoter or suppressor in the malignant processes of multiple cancers. However, its proliferative function in hepatocellular carcinoma (HCC) has been poorly st...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406114/ https://www.ncbi.nlm.nih.gov/pubmed/37554583 http://dx.doi.org/10.2147/JHC.S418049 |
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author | Lu, Xun Yuan, Yue Cai, Ning Rao, Dean Chen, Min Chen, Xiaoping Zhang, Bixiang Liang, Huifang Zhang, Lei |
author_facet | Lu, Xun Yuan, Yue Cai, Ning Rao, Dean Chen, Min Chen, Xiaoping Zhang, Bixiang Liang, Huifang Zhang, Lei |
author_sort | Lu, Xun |
collection | PubMed |
description | PURPOSE: Tripartite motif containing 55 (TRIM55) is a member of the TRIM family and functions as an E3 ubiquitin ligase. It acts as a cancer promoter or suppressor in the malignant processes of multiple cancers. However, its proliferative function in hepatocellular carcinoma (HCC) has been poorly studied, and its underlying molecular mechanism remains unclear. In the present study, we investigated the role of TRIM55 in HCC and its mechanism of promoting HCC proliferation. MATERIALS AND METHODS: Protein expression levels of TRIM55 were measured in paired HCC and normal tissue samples using immunohistochemical (IHC) staining. The correlation between TRIM55 and clinical features was evaluated by statistical analysis. At the same time, overexpression and knockdown experiments, cycloheximide (CHX) interference experiments, ubiquitination, co-immunoprecipitation and immunofluorescence staining experiments, as well as animal experiments were used to evaluate the potential mechanism that TRIM55 promotes proliferation of hepatocellular carcinoma in vitro and in vivo. RESULTS: TRIM55 expression in HCC specimens was higher compared with the corresponding non-tumor tissues. The overall survival and disease-free survival time of patients with high TRIM55 expression were shorter than those with low expression of TRIM55. Functionally, TRIM55 promoted the proliferation of HCC cells and accelerated the growth of HCC xenografts. Mechanistically, TRIM55 interacted with thyroid receptor interacting protein 6 (TRIP6) and regulate its stability by influencing the ubiquitination process, thereby affecting the Wnt signaling pathway. CONCLUSION: Our results indicate that TRIM55 promotes HCC proliferation by activating Wnt signaling pathways by stabilizing TRIP6. Therefore, targeting TRIM55 may be an effective therapeutic strategy to inhibit HCC growth. |
format | Online Article Text |
id | pubmed-10406114 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-104061142023-08-08 TRIM55 Promotes Proliferation of Hepatocellular Carcinoma Through Stabilizing TRIP6 to Activate Wnt/β-Catenin Signaling Lu, Xun Yuan, Yue Cai, Ning Rao, Dean Chen, Min Chen, Xiaoping Zhang, Bixiang Liang, Huifang Zhang, Lei J Hepatocell Carcinoma Original Research PURPOSE: Tripartite motif containing 55 (TRIM55) is a member of the TRIM family and functions as an E3 ubiquitin ligase. It acts as a cancer promoter or suppressor in the malignant processes of multiple cancers. However, its proliferative function in hepatocellular carcinoma (HCC) has been poorly studied, and its underlying molecular mechanism remains unclear. In the present study, we investigated the role of TRIM55 in HCC and its mechanism of promoting HCC proliferation. MATERIALS AND METHODS: Protein expression levels of TRIM55 were measured in paired HCC and normal tissue samples using immunohistochemical (IHC) staining. The correlation between TRIM55 and clinical features was evaluated by statistical analysis. At the same time, overexpression and knockdown experiments, cycloheximide (CHX) interference experiments, ubiquitination, co-immunoprecipitation and immunofluorescence staining experiments, as well as animal experiments were used to evaluate the potential mechanism that TRIM55 promotes proliferation of hepatocellular carcinoma in vitro and in vivo. RESULTS: TRIM55 expression in HCC specimens was higher compared with the corresponding non-tumor tissues. The overall survival and disease-free survival time of patients with high TRIM55 expression were shorter than those with low expression of TRIM55. Functionally, TRIM55 promoted the proliferation of HCC cells and accelerated the growth of HCC xenografts. Mechanistically, TRIM55 interacted with thyroid receptor interacting protein 6 (TRIP6) and regulate its stability by influencing the ubiquitination process, thereby affecting the Wnt signaling pathway. CONCLUSION: Our results indicate that TRIM55 promotes HCC proliferation by activating Wnt signaling pathways by stabilizing TRIP6. Therefore, targeting TRIM55 may be an effective therapeutic strategy to inhibit HCC growth. Dove 2023-08-03 /pmc/articles/PMC10406114/ /pubmed/37554583 http://dx.doi.org/10.2147/JHC.S418049 Text en © 2023 Lu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Lu, Xun Yuan, Yue Cai, Ning Rao, Dean Chen, Min Chen, Xiaoping Zhang, Bixiang Liang, Huifang Zhang, Lei TRIM55 Promotes Proliferation of Hepatocellular Carcinoma Through Stabilizing TRIP6 to Activate Wnt/β-Catenin Signaling |
title | TRIM55 Promotes Proliferation of Hepatocellular Carcinoma Through Stabilizing TRIP6 to Activate Wnt/β-Catenin Signaling |
title_full | TRIM55 Promotes Proliferation of Hepatocellular Carcinoma Through Stabilizing TRIP6 to Activate Wnt/β-Catenin Signaling |
title_fullStr | TRIM55 Promotes Proliferation of Hepatocellular Carcinoma Through Stabilizing TRIP6 to Activate Wnt/β-Catenin Signaling |
title_full_unstemmed | TRIM55 Promotes Proliferation of Hepatocellular Carcinoma Through Stabilizing TRIP6 to Activate Wnt/β-Catenin Signaling |
title_short | TRIM55 Promotes Proliferation of Hepatocellular Carcinoma Through Stabilizing TRIP6 to Activate Wnt/β-Catenin Signaling |
title_sort | trim55 promotes proliferation of hepatocellular carcinoma through stabilizing trip6 to activate wnt/β-catenin signaling |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406114/ https://www.ncbi.nlm.nih.gov/pubmed/37554583 http://dx.doi.org/10.2147/JHC.S418049 |
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