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Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma
BACKGROUND: PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC. METHODS: PR55α expressions in HCC tissues and paired healthy liver samples w...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885213/ https://www.ncbi.nlm.nih.gov/pubmed/33588847 http://dx.doi.org/10.1186/s12935-021-01796-0 |
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author | Zhao, JiangSheng Chen, GuoFeng Li, Jingqi Liu, Shiqi Jin, Quan Zhang, ZhengWei Qi, Fuzhen Zhang, JianHuai Xu, JianBo |
author_facet | Zhao, JiangSheng Chen, GuoFeng Li, Jingqi Liu, Shiqi Jin, Quan Zhang, ZhengWei Qi, Fuzhen Zhang, JianHuai Xu, JianBo |
author_sort | Zhao, JiangSheng |
collection | PubMed |
description | BACKGROUND: PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC. METHODS: PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing. RESULTS: PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2. CONCLUSIONS: This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC. |
format | Online Article Text |
id | pubmed-7885213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-78852132021-02-17 Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma Zhao, JiangSheng Chen, GuoFeng Li, Jingqi Liu, Shiqi Jin, Quan Zhang, ZhengWei Qi, Fuzhen Zhang, JianHuai Xu, JianBo Cancer Cell Int Primary Research BACKGROUND: PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC. METHODS: PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing. RESULTS: PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2. CONCLUSIONS: This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC. BioMed Central 2021-02-15 /pmc/articles/PMC7885213/ /pubmed/33588847 http://dx.doi.org/10.1186/s12935-021-01796-0 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Zhao, JiangSheng Chen, GuoFeng Li, Jingqi Liu, Shiqi Jin, Quan Zhang, ZhengWei Qi, Fuzhen Zhang, JianHuai Xu, JianBo Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma |
title | Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma |
title_full | Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma |
title_fullStr | Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma |
title_full_unstemmed | Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma |
title_short | Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma |
title_sort | loss of pr55α promotes proliferation and metastasis by activating mapk/akt signaling in hepatocellular carcinoma |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885213/ https://www.ncbi.nlm.nih.gov/pubmed/33588847 http://dx.doi.org/10.1186/s12935-021-01796-0 |
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