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...
Autores principales: | , , , , , , , |
---|---|
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 |