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Dysregulation of PLOD2 Promotes Tumor Metastasis and Invasion in Hepatocellular Carcinoma

BACKGROUND AND AIMS: Metastasis is a major factor associated with high recurrence and mortality in hepatocellular carcinoma (HCC) patients while the underlying mechanism of metastasis remains elusive. In our study, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was shown to be involved i...

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Autores principales: Li, Keren, Niu, Yi, Li, Kai, Zhong, Chengrui, Qiu, Zhiyu, Yuan, Yichuan, Shi, Yunxing, Lin, Zhu, Huang, Zhenkun, Zuo, Dinglan, Yuan, Yunfei, Li, Binkui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: XIA & HE Publishing Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10412693/
https://www.ncbi.nlm.nih.gov/pubmed/37577214
http://dx.doi.org/10.14218/JCTH.2022.00401
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author Li, Keren
Niu, Yi
Li, Kai
Zhong, Chengrui
Qiu, Zhiyu
Yuan, Yichuan
Shi, Yunxing
Lin, Zhu
Huang, Zhenkun
Zuo, Dinglan
Yuan, Yunfei
Li, Binkui
author_facet Li, Keren
Niu, Yi
Li, Kai
Zhong, Chengrui
Qiu, Zhiyu
Yuan, Yichuan
Shi, Yunxing
Lin, Zhu
Huang, Zhenkun
Zuo, Dinglan
Yuan, Yunfei
Li, Binkui
author_sort Li, Keren
collection PubMed
description BACKGROUND AND AIMS: Metastasis is a major factor associated with high recurrence and mortality in hepatocellular carcinoma (HCC) patients while the underlying mechanism of metastasis remains elusive. In our study, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was shown to be involved in the process of metastasis in HCC. METHODS: The Cancer Genome Atlas (TCGA) database and HCC tissue microarrays were used to evaluate the expression of genes. In vitro migration, invasion, in vivo subcutaneous tumor model and in vivo lung metastasis assays were used to determine the role of PLOD2 in tumor growth and metastasis in HCC. RNA sequencing and gene set enrichment analysis were performed to uncover the downstream factor of PLOD2 in HCC cells. A luciferase reporter assay was performed to evaluate the interaction between PLOD2 and interferon regulatory factor 5 (IRF5). RESULTS: The expression of PLOD2 in HCC tissues was higher than that in adjacent tissues, and increased PLOD2 expression was often found in advanced tumors and was correlated with poor prognosis in HCC patients. In vitro experiments, knockdown of PLOD2 reduced the migration and invasion of human HCC cells. Loss of PLOD2 suppressed human HCC growth and metastasis in a subcutaneous tumor model and a lung metastasis model. Baculoviral IAP repeat containing 3 (BIRC3) was proven to be the downstream factor of PLOD2 in human HCC cells. In addition, PLOD2 was transcriptionally regulated by IRF5 in HCC cells. CONCLUSIONS: High expression of PLOD2 was regulated by IRF5, which was correlated with the poor survival of HCC patients. PLOD2 enhanced HCC metastasis via BIRC3, suggesting that PLOD2 might be a valuable prognostic biomarker for HCC treatment.
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spelling pubmed-104126932023-08-11 Dysregulation of PLOD2 Promotes Tumor Metastasis and Invasion in Hepatocellular Carcinoma Li, Keren Niu, Yi Li, Kai Zhong, Chengrui Qiu, Zhiyu Yuan, Yichuan Shi, Yunxing Lin, Zhu Huang, Zhenkun Zuo, Dinglan Yuan, Yunfei Li, Binkui J Clin Transl Hepatol Original Article BACKGROUND AND AIMS: Metastasis is a major factor associated with high recurrence and mortality in hepatocellular carcinoma (HCC) patients while the underlying mechanism of metastasis remains elusive. In our study, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was shown to be involved in the process of metastasis in HCC. METHODS: The Cancer Genome Atlas (TCGA) database and HCC tissue microarrays were used to evaluate the expression of genes. In vitro migration, invasion, in vivo subcutaneous tumor model and in vivo lung metastasis assays were used to determine the role of PLOD2 in tumor growth and metastasis in HCC. RNA sequencing and gene set enrichment analysis were performed to uncover the downstream factor of PLOD2 in HCC cells. A luciferase reporter assay was performed to evaluate the interaction between PLOD2 and interferon regulatory factor 5 (IRF5). RESULTS: The expression of PLOD2 in HCC tissues was higher than that in adjacent tissues, and increased PLOD2 expression was often found in advanced tumors and was correlated with poor prognosis in HCC patients. In vitro experiments, knockdown of PLOD2 reduced the migration and invasion of human HCC cells. Loss of PLOD2 suppressed human HCC growth and metastasis in a subcutaneous tumor model and a lung metastasis model. Baculoviral IAP repeat containing 3 (BIRC3) was proven to be the downstream factor of PLOD2 in human HCC cells. In addition, PLOD2 was transcriptionally regulated by IRF5 in HCC cells. CONCLUSIONS: High expression of PLOD2 was regulated by IRF5, which was correlated with the poor survival of HCC patients. PLOD2 enhanced HCC metastasis via BIRC3, suggesting that PLOD2 might be a valuable prognostic biomarker for HCC treatment. XIA & HE Publishing Inc. 2023-10-28 2023-04-21 /pmc/articles/PMC10412693/ /pubmed/37577214 http://dx.doi.org/10.14218/JCTH.2022.00401 Text en © 2023 Authors. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Li, Keren
Niu, Yi
Li, Kai
Zhong, Chengrui
Qiu, Zhiyu
Yuan, Yichuan
Shi, Yunxing
Lin, Zhu
Huang, Zhenkun
Zuo, Dinglan
Yuan, Yunfei
Li, Binkui
Dysregulation of PLOD2 Promotes Tumor Metastasis and Invasion in Hepatocellular Carcinoma
title Dysregulation of PLOD2 Promotes Tumor Metastasis and Invasion in Hepatocellular Carcinoma
title_full Dysregulation of PLOD2 Promotes Tumor Metastasis and Invasion in Hepatocellular Carcinoma
title_fullStr Dysregulation of PLOD2 Promotes Tumor Metastasis and Invasion in Hepatocellular Carcinoma
title_full_unstemmed Dysregulation of PLOD2 Promotes Tumor Metastasis and Invasion in Hepatocellular Carcinoma
title_short Dysregulation of PLOD2 Promotes Tumor Metastasis and Invasion in Hepatocellular Carcinoma
title_sort dysregulation of plod2 promotes tumor metastasis and invasion in hepatocellular carcinoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10412693/
https://www.ncbi.nlm.nih.gov/pubmed/37577214
http://dx.doi.org/10.14218/JCTH.2022.00401
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