Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: You, Yu, Wen, Diguang, Zeng, Lu, Lu, Jiao, Xiao, Xiao, Chen, Yucheng, Song, Hua, Liu, Zuojin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2022
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
_version_ 1784768671182225408
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
work_keys_str_mv AT youyu alkbh5map3k8axisregulatespdl1macrophageinfiltrationandpromoteshepatocellularcarcinomaprogression
AT wendiguang alkbh5map3k8axisregulatespdl1macrophageinfiltrationandpromoteshepatocellularcarcinomaprogression
AT zenglu alkbh5map3k8axisregulatespdl1macrophageinfiltrationandpromoteshepatocellularcarcinomaprogression
AT lujiao alkbh5map3k8axisregulatespdl1macrophageinfiltrationandpromoteshepatocellularcarcinomaprogression
AT xiaoxiao alkbh5map3k8axisregulatespdl1macrophageinfiltrationandpromoteshepatocellularcarcinomaprogression
AT chenyucheng alkbh5map3k8axisregulatespdl1macrophageinfiltrationandpromoteshepatocellularcarcinomaprogression
AT songhua alkbh5map3k8axisregulatespdl1macrophageinfiltrationandpromoteshepatocellularcarcinomaprogression
AT liuzuojin alkbh5map3k8axisregulatespdl1macrophageinfiltrationandpromoteshepatocellularcarcinomaprogression