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FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma

F-box proteins are critical for malignancy because they control the turnover of key proteins that govern multiple cellular processes. F-box protein 9 (FBXO9) belongs to the F-box protein family and exhibits oncogenic properties in hematological malignancies. However, the function and molecular mecha...

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Autores principales: Wang, Zhenyu, Chen, Xiaoxia, Zhou, Lianer, Zhao, Xinge, Ge, Chao, Zhao, Fangyu, Xie, Haiyang, Chen, Taoyang, Tian, Hua, Li, Hong, Li, Jinjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280481/
https://www.ncbi.nlm.nih.gov/pubmed/35847937
http://dx.doi.org/10.3389/fonc.2022.930220
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author Wang, Zhenyu
Chen, Xiaoxia
Zhou, Lianer
Zhao, Xinge
Ge, Chao
Zhao, Fangyu
Xie, Haiyang
Chen, Taoyang
Tian, Hua
Li, Hong
Li, Jinjun
author_facet Wang, Zhenyu
Chen, Xiaoxia
Zhou, Lianer
Zhao, Xinge
Ge, Chao
Zhao, Fangyu
Xie, Haiyang
Chen, Taoyang
Tian, Hua
Li, Hong
Li, Jinjun
author_sort Wang, Zhenyu
collection PubMed
description F-box proteins are critical for malignancy because they control the turnover of key proteins that govern multiple cellular processes. F-box protein 9 (FBXO9) belongs to the F-box protein family and exhibits oncogenic properties in hematological malignancies. However, the function and molecular mechanism of FBXO9 in hepatocellular carcinoma (HCC) remain unclear. Here, we report that FBXO9 was remarkably overexpressed in HCC. Loss- and gain-of-function experiments showed that FBXO9 facilitates HCC cell proliferation and metastasis both in vitro and in vivo. Mechanistically, as a direct upstream transcription factor, FBXO9 is regulated by zinc finger protein 143 (ZNF143) and accelerates tumor growth and metastasis by targeting the F-box and WD repeat domain containing 7 (FBXW7) for ubiquitination and degradation. Additionally, we found that with FBXO9 knockdown, HCC cells were more sensitive to treatment with lenvatinib and sorafenib. In summary, our results demonstrate that a ZNF143-FBXO9-FBXW7 signaling regulatory axis may be involved in tumor progression in HCC, and suggest that FBXO9 could be a potential biomarker and therapeutic target for HCC.
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spelling pubmed-92804812022-07-15 FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma Wang, Zhenyu Chen, Xiaoxia Zhou, Lianer Zhao, Xinge Ge, Chao Zhao, Fangyu Xie, Haiyang Chen, Taoyang Tian, Hua Li, Hong Li, Jinjun Front Oncol Oncology F-box proteins are critical for malignancy because they control the turnover of key proteins that govern multiple cellular processes. F-box protein 9 (FBXO9) belongs to the F-box protein family and exhibits oncogenic properties in hematological malignancies. However, the function and molecular mechanism of FBXO9 in hepatocellular carcinoma (HCC) remain unclear. Here, we report that FBXO9 was remarkably overexpressed in HCC. Loss- and gain-of-function experiments showed that FBXO9 facilitates HCC cell proliferation and metastasis both in vitro and in vivo. Mechanistically, as a direct upstream transcription factor, FBXO9 is regulated by zinc finger protein 143 (ZNF143) and accelerates tumor growth and metastasis by targeting the F-box and WD repeat domain containing 7 (FBXW7) for ubiquitination and degradation. Additionally, we found that with FBXO9 knockdown, HCC cells were more sensitive to treatment with lenvatinib and sorafenib. In summary, our results demonstrate that a ZNF143-FBXO9-FBXW7 signaling regulatory axis may be involved in tumor progression in HCC, and suggest that FBXO9 could be a potential biomarker and therapeutic target for HCC. Frontiers Media S.A. 2022-06-30 /pmc/articles/PMC9280481/ /pubmed/35847937 http://dx.doi.org/10.3389/fonc.2022.930220 Text en Copyright © 2022 Wang, Chen, Zhou, Zhao, Ge, Zhao, Xie, Chen, Tian, Li and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wang, Zhenyu
Chen, Xiaoxia
Zhou, Lianer
Zhao, Xinge
Ge, Chao
Zhao, Fangyu
Xie, Haiyang
Chen, Taoyang
Tian, Hua
Li, Hong
Li, Jinjun
FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma
title FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma
title_full FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma
title_fullStr FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma
title_full_unstemmed FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma
title_short FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma
title_sort fbxo9 mediates the cancer-promoting effects of znf143 by degrading fbxw7 and facilitates drug resistance in hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280481/
https://www.ncbi.nlm.nih.gov/pubmed/35847937
http://dx.doi.org/10.3389/fonc.2022.930220
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