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ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression
Hepatocellular carcinoma is one of the most common malignant tumors.M6A is a novel epigenetic modification that have been emerged as vital regulators for the progression of HCC. However, the regulatory role, clinical significance and the details of the modification, such as the impact on the local t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379398/ https://www.ncbi.nlm.nih.gov/pubmed/35982895 http://dx.doi.org/10.7150/ijbs.70149 |
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author | You, Yu Wen, Diguang Zeng, Lu Lu, Jiao Xiao, Xiao Chen, Yucheng Song, Hua Liu, Zuojin |
author_facet | You, Yu Wen, Diguang Zeng, Lu Lu, Jiao Xiao, Xiao Chen, Yucheng Song, Hua Liu, Zuojin |
author_sort | You, Yu |
collection | PubMed |
description | Hepatocellular carcinoma is one of the most common malignant tumors.M6A is a novel epigenetic modification that have been emerged as vital regulators for the progression of HCC. However, the regulatory role, clinical significance and the details of the modification, such as the impact on the local tumor environment, remain largely unclear. Our study showed that ALKBH5 was highly expressed in HCC and high ALKBH5 expression predicted a worse prognosis of HCC patients. Prediction of ALKBH5 function by tissue samples and single cell sequencing Gene Set Variation Analysis. Primary CD3 + T lymphocytes and bone marrow-derived macrophages were used to evaluate the effect of ALKBH5 on immune microenvironment. The results indicated that ALKBH5 promote HCC cell proliferation, metastasis and PD-L1+macrophage recruitment. Mechanistically the results showed that ALKBH5 regulates MAP3K8 expression in a m6A dependent manner which mediates the proliferation and metastasis of HCC cells. ALKBH5 also promotes the activation of JNK and ERK pathways through upregulating MAP3K8, thus regulating the expression of IL-8 and promoting macrophage recruitment. Taken together, these data show that ALKBH5 promotes HCC growth, metastasis and macrophage recruitment through ALKBH5/MAP3K8 axis and it may serve as a potential diagnostic marker and target for treatment of HCC patients. |
format | Online Article Text |
id | pubmed-9379398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-93793982022-08-17 ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression You, Yu Wen, Diguang Zeng, Lu Lu, Jiao Xiao, Xiao Chen, Yucheng Song, Hua Liu, Zuojin Int J Biol Sci Research Paper Hepatocellular carcinoma is one of the most common malignant tumors.M6A is a novel epigenetic modification that have been emerged as vital regulators for the progression of HCC. However, the regulatory role, clinical significance and the details of the modification, such as the impact on the local tumor environment, remain largely unclear. Our study showed that ALKBH5 was highly expressed in HCC and high ALKBH5 expression predicted a worse prognosis of HCC patients. Prediction of ALKBH5 function by tissue samples and single cell sequencing Gene Set Variation Analysis. Primary CD3 + T lymphocytes and bone marrow-derived macrophages were used to evaluate the effect of ALKBH5 on immune microenvironment. The results indicated that ALKBH5 promote HCC cell proliferation, metastasis and PD-L1+macrophage recruitment. Mechanistically the results showed that ALKBH5 regulates MAP3K8 expression in a m6A dependent manner which mediates the proliferation and metastasis of HCC cells. ALKBH5 also promotes the activation of JNK and ERK pathways through upregulating MAP3K8, thus regulating the expression of IL-8 and promoting macrophage recruitment. Taken together, these data show that ALKBH5 promotes HCC growth, metastasis and macrophage recruitment through ALKBH5/MAP3K8 axis and it may serve as a potential diagnostic marker and target for treatment of HCC patients. Ivyspring International Publisher 2022-08-01 /pmc/articles/PMC9379398/ /pubmed/35982895 http://dx.doi.org/10.7150/ijbs.70149 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper You, Yu Wen, Diguang Zeng, Lu Lu, Jiao Xiao, Xiao Chen, Yucheng Song, Hua Liu, Zuojin ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression |
title | ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression |
title_full | ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression |
title_fullStr | ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression |
title_full_unstemmed | ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression |
title_short | ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression |
title_sort | alkbh5/map3k8 axis regulates pd-l1+ macrophage infiltration and promotes hepatocellular carcinoma progression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379398/ https://www.ncbi.nlm.nih.gov/pubmed/35982895 http://dx.doi.org/10.7150/ijbs.70149 |
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