Cargando…

Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway

BACKGROUND: The study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells. METHODS: Forty patients with HCC were included in the study. Bioinformatic analysis was used to analyze the clinical relevance of HIG2 expression in HCC...

Descripción completa

Detalles Bibliográficos
Autores principales: Cui, Chuanbao, Fu, Kaiwen, Yang, Lu, Wu, Shuzhi, Cen, Zuojie, Meng, Xingxing, Huang, Qiongguang, Xie, Zhichun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542136/
https://www.ncbi.nlm.nih.gov/pubmed/31142329
http://dx.doi.org/10.1186/s13046-019-1233-9
_version_ 1783422890634379264
author Cui, Chuanbao
Fu, Kaiwen
Yang, Lu
Wu, Shuzhi
Cen, Zuojie
Meng, Xingxing
Huang, Qiongguang
Xie, Zhichun
author_facet Cui, Chuanbao
Fu, Kaiwen
Yang, Lu
Wu, Shuzhi
Cen, Zuojie
Meng, Xingxing
Huang, Qiongguang
Xie, Zhichun
author_sort Cui, Chuanbao
collection PubMed
description BACKGROUND: The study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells. METHODS: Forty patients with HCC were included in the study. Bioinformatic analysis was used to analyze the clinical relevance of HIG2 expression in HCC tissue samples. Immunohistochemistry was employed to determine the expression of target proteins in tumor tissues. Hepatic HepG2 and SMMC-7721 cells were transfected with HIG2-targeting siRNA with Lipofectamine 2000. qRT-PCR was carried out to determine gene expression levels, while Western blotting was used to determine protein expression. A CCK-8 assay was performed to detect proliferation of cells, while migration and invasion of cells were studied by Transwell assay. Flow cytometry was carried out to detect surface markers and effector molecules in Nature killercells, as well as the killing effect of NK cells. RESULTS: HIG2 expression was upregulated in HCC. Silencing of HIG2 suppressed HCC cell migration and invasion. The killing effect of NK cells on HCC cells was enhanced after HIG2 was silenced in HCC cells. Conditioned media from HIG2-silenced SMMC-7721 cells inhibited the phenotype and function of NK cells. HCC cells with silenced expression of HIG2 modulated the activity of NK cells via STAT3. HIG2 promoted the evasion of HCC cells from killing by NK cells through upregulation of IL-10 expression. CONCLUSION: The study demonstrates that HIG2 activates the STAT3 signaling pathway in NK cells by promoting IL-10 release by HCC cells, thereby inhibiting the killing activity of NK cells, and subsequently promoting the recurrence and metastasis of HCC.
format Online
Article
Text
id pubmed-6542136
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-65421362019-06-03 Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway Cui, Chuanbao Fu, Kaiwen Yang, Lu Wu, Shuzhi Cen, Zuojie Meng, Xingxing Huang, Qiongguang Xie, Zhichun J Exp Clin Cancer Res Research BACKGROUND: The study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells. METHODS: Forty patients with HCC were included in the study. Bioinformatic analysis was used to analyze the clinical relevance of HIG2 expression in HCC tissue samples. Immunohistochemistry was employed to determine the expression of target proteins in tumor tissues. Hepatic HepG2 and SMMC-7721 cells were transfected with HIG2-targeting siRNA with Lipofectamine 2000. qRT-PCR was carried out to determine gene expression levels, while Western blotting was used to determine protein expression. A CCK-8 assay was performed to detect proliferation of cells, while migration and invasion of cells were studied by Transwell assay. Flow cytometry was carried out to detect surface markers and effector molecules in Nature killercells, as well as the killing effect of NK cells. RESULTS: HIG2 expression was upregulated in HCC. Silencing of HIG2 suppressed HCC cell migration and invasion. The killing effect of NK cells on HCC cells was enhanced after HIG2 was silenced in HCC cells. Conditioned media from HIG2-silenced SMMC-7721 cells inhibited the phenotype and function of NK cells. HCC cells with silenced expression of HIG2 modulated the activity of NK cells via STAT3. HIG2 promoted the evasion of HCC cells from killing by NK cells through upregulation of IL-10 expression. CONCLUSION: The study demonstrates that HIG2 activates the STAT3 signaling pathway in NK cells by promoting IL-10 release by HCC cells, thereby inhibiting the killing activity of NK cells, and subsequently promoting the recurrence and metastasis of HCC. BioMed Central 2019-05-29 /pmc/articles/PMC6542136/ /pubmed/31142329 http://dx.doi.org/10.1186/s13046-019-1233-9 Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.
spellingShingle Research
Cui, Chuanbao
Fu, Kaiwen
Yang, Lu
Wu, Shuzhi
Cen, Zuojie
Meng, Xingxing
Huang, Qiongguang
Xie, Zhichun
Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway
title Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway
title_full Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway
title_fullStr Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway
title_full_unstemmed Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway
title_short Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway
title_sort hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-stat3 signaling pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542136/
https://www.ncbi.nlm.nih.gov/pubmed/31142329
http://dx.doi.org/10.1186/s13046-019-1233-9
work_keys_str_mv AT cuichuanbao hypoxiainduciblegene2promotestheimmuneescapeofhepatocellularcarcinomafromnaturekillercellsthroughtheinterleukin10stat3signalingpathway
AT fukaiwen hypoxiainduciblegene2promotestheimmuneescapeofhepatocellularcarcinomafromnaturekillercellsthroughtheinterleukin10stat3signalingpathway
AT yanglu hypoxiainduciblegene2promotestheimmuneescapeofhepatocellularcarcinomafromnaturekillercellsthroughtheinterleukin10stat3signalingpathway
AT wushuzhi hypoxiainduciblegene2promotestheimmuneescapeofhepatocellularcarcinomafromnaturekillercellsthroughtheinterleukin10stat3signalingpathway
AT cenzuojie hypoxiainduciblegene2promotestheimmuneescapeofhepatocellularcarcinomafromnaturekillercellsthroughtheinterleukin10stat3signalingpathway
AT mengxingxing hypoxiainduciblegene2promotestheimmuneescapeofhepatocellularcarcinomafromnaturekillercellsthroughtheinterleukin10stat3signalingpathway
AT huangqiongguang hypoxiainduciblegene2promotestheimmuneescapeofhepatocellularcarcinomafromnaturekillercellsthroughtheinterleukin10stat3signalingpathway
AT xiezhichun hypoxiainduciblegene2promotestheimmuneescapeofhepatocellularcarcinomafromnaturekillercellsthroughtheinterleukin10stat3signalingpathway