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RIG-I Promotes Cell Death in Hepatocellular Carcinoma by Inducing M1 Polarization of Perineal Macrophages Through the RIG-I/MAVS/NF-κB Pathway

BACKGROUND: The development and metastasis of cancer cells are regulated by tumor-associated macrophages (TAMs) present in the surrounding tumor microenvironment. RIG-I is a key pathogen recognition receptor against RNA viruses that regulates innate immunity in cancer progression. Till now, the mech...

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Autores principales: Zhou, Bei, Li, Cuiping, Yang, Yun, Wang, Zhuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493023/
https://www.ncbi.nlm.nih.gov/pubmed/32982277
http://dx.doi.org/10.2147/OTT.S258450
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author Zhou, Bei
Li, Cuiping
Yang, Yun
Wang, Zhuo
author_facet Zhou, Bei
Li, Cuiping
Yang, Yun
Wang, Zhuo
author_sort Zhou, Bei
collection PubMed
description BACKGROUND: The development and metastasis of cancer cells are regulated by tumor-associated macrophages (TAMs) present in the surrounding tumor microenvironment. RIG-I is a key pathogen recognition receptor against RNA viruses that regulates innate immunity in cancer progression. Till now, the mechanism of RIG-I regulation of the polarization of TAMs in the progression of hepatocellular carcinoma (HCC) has not been understood. MATERIALS AND METHODS: Levels of RIG-I and the key proteins in the NF-κB pathway in HCC and paired paracancerous tissues were detected by Western blotting. The transfection efficiency of RIG-I was observed by fluorescence microscopy. The M1 and M2 markers were detected by real-time polymerase chain reaction and FACS assays. Apoptosis of RIG-I lentivirus-infected HCC cells was detected by flow cytometry assay. Death of Hepa1-6 and H22 cells was analyzed by lactate dehydrogenase releasing assay. RESULTS: The level of RIG-I was decreased in HCC tissues as compared to that in the paired paracancerous tissues. Overexpression of RIG-I in mouse peritoneal macrophages increased the expression of the biomarkers CD16/32 and CD11c associated with M1 macrophages. The relative levels of IL-1β, TNF-α, IL-6, and iNOS were significantly increased in RIG-I lentivirus-infected macrophages, whereas the levels of Arg-1 and IL-10 were not significantly different in RIG-I-overexpressed peritoneal macrophages. Moreover, overexpression of RIG-I in peritoneal macrophages promoted apoptosis of Hepa1-6 and H22 cells. Furthermore, overexpression of RIG-I increased the levels of phosphorylated p65 and p-IκB and decreased the level of IκB in peritoneal macrophages. Importantly, the expression of MAVS and TRAF2 was significantly increased in RIG-I lentivirus-infected macrophages. CONCLUSION: Our results demonstrate that overexpression of RIG-I promoted apoptosis and death of HCC cells. Moreover, RIG-I promoted the polarization of M1 through the RIG-I/MAVS/TRAF2/NF-κB pathway in mice peritoneal macrophages, suggesting that RIG-I may be a novel target in the immunotherapy of HCC.
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spelling pubmed-74930232020-09-24 RIG-I Promotes Cell Death in Hepatocellular Carcinoma by Inducing M1 Polarization of Perineal Macrophages Through the RIG-I/MAVS/NF-κB Pathway Zhou, Bei Li, Cuiping Yang, Yun Wang, Zhuo Onco Targets Ther Original Research BACKGROUND: The development and metastasis of cancer cells are regulated by tumor-associated macrophages (TAMs) present in the surrounding tumor microenvironment. RIG-I is a key pathogen recognition receptor against RNA viruses that regulates innate immunity in cancer progression. Till now, the mechanism of RIG-I regulation of the polarization of TAMs in the progression of hepatocellular carcinoma (HCC) has not been understood. MATERIALS AND METHODS: Levels of RIG-I and the key proteins in the NF-κB pathway in HCC and paired paracancerous tissues were detected by Western blotting. The transfection efficiency of RIG-I was observed by fluorescence microscopy. The M1 and M2 markers were detected by real-time polymerase chain reaction and FACS assays. Apoptosis of RIG-I lentivirus-infected HCC cells was detected by flow cytometry assay. Death of Hepa1-6 and H22 cells was analyzed by lactate dehydrogenase releasing assay. RESULTS: The level of RIG-I was decreased in HCC tissues as compared to that in the paired paracancerous tissues. Overexpression of RIG-I in mouse peritoneal macrophages increased the expression of the biomarkers CD16/32 and CD11c associated with M1 macrophages. The relative levels of IL-1β, TNF-α, IL-6, and iNOS were significantly increased in RIG-I lentivirus-infected macrophages, whereas the levels of Arg-1 and IL-10 were not significantly different in RIG-I-overexpressed peritoneal macrophages. Moreover, overexpression of RIG-I in peritoneal macrophages promoted apoptosis of Hepa1-6 and H22 cells. Furthermore, overexpression of RIG-I increased the levels of phosphorylated p65 and p-IκB and decreased the level of IκB in peritoneal macrophages. Importantly, the expression of MAVS and TRAF2 was significantly increased in RIG-I lentivirus-infected macrophages. CONCLUSION: Our results demonstrate that overexpression of RIG-I promoted apoptosis and death of HCC cells. Moreover, RIG-I promoted the polarization of M1 through the RIG-I/MAVS/TRAF2/NF-κB pathway in mice peritoneal macrophages, suggesting that RIG-I may be a novel target in the immunotherapy of HCC. Dove 2020-09-03 /pmc/articles/PMC7493023/ /pubmed/32982277 http://dx.doi.org/10.2147/OTT.S258450 Text en © 2020 Zhou et al. http://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/). 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
Zhou, Bei
Li, Cuiping
Yang, Yun
Wang, Zhuo
RIG-I Promotes Cell Death in Hepatocellular Carcinoma by Inducing M1 Polarization of Perineal Macrophages Through the RIG-I/MAVS/NF-κB Pathway
title RIG-I Promotes Cell Death in Hepatocellular Carcinoma by Inducing M1 Polarization of Perineal Macrophages Through the RIG-I/MAVS/NF-κB Pathway
title_full RIG-I Promotes Cell Death in Hepatocellular Carcinoma by Inducing M1 Polarization of Perineal Macrophages Through the RIG-I/MAVS/NF-κB Pathway
title_fullStr RIG-I Promotes Cell Death in Hepatocellular Carcinoma by Inducing M1 Polarization of Perineal Macrophages Through the RIG-I/MAVS/NF-κB Pathway
title_full_unstemmed RIG-I Promotes Cell Death in Hepatocellular Carcinoma by Inducing M1 Polarization of Perineal Macrophages Through the RIG-I/MAVS/NF-κB Pathway
title_short RIG-I Promotes Cell Death in Hepatocellular Carcinoma by Inducing M1 Polarization of Perineal Macrophages Through the RIG-I/MAVS/NF-κB Pathway
title_sort rig-i promotes cell death in hepatocellular carcinoma by inducing m1 polarization of perineal macrophages through the rig-i/mavs/nf-κb pathway
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493023/
https://www.ncbi.nlm.nih.gov/pubmed/32982277
http://dx.doi.org/10.2147/OTT.S258450
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