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The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer
BACKGROUND: Ovarian cancer (OC) is one of the most lethal gynecologic cancers. Growing evidence has proven that CDK4/6 plays a key role in tumor immunity and the prognosis of many cancers. However, the expression and function of CDK4/6 in OC remain unclear. Therefore, we aimed to explore the influen...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795791/ https://www.ncbi.nlm.nih.gov/pubmed/35095879 http://dx.doi.org/10.3389/fimmu.2021.799171 |
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author | Liu, Chen Huang, Yuhan Cui, Yaoyuan Zhou, Jun Qin, Xu Zhang, Li Li, Xi Li, Yuan Guo, Ensong Yang, Bin Li, Xi Fan, Junpeng Li, Xiong Fu, Yu Liu, Si Hu, Dianxing Xiao, Rourou Wang, Zizhuo Dou, Yingyu Wang, Wei Li, Wenting Yang, Xiaohang Liu, Jingbo Peng, Wenju Qin, Tianyu You, Lixin Lu, Funian Sun, Chaoyang |
author_facet | Liu, Chen Huang, Yuhan Cui, Yaoyuan Zhou, Jun Qin, Xu Zhang, Li Li, Xi Li, Yuan Guo, Ensong Yang, Bin Li, Xi Fan, Junpeng Li, Xiong Fu, Yu Liu, Si Hu, Dianxing Xiao, Rourou Wang, Zizhuo Dou, Yingyu Wang, Wei Li, Wenting Yang, Xiaohang Liu, Jingbo Peng, Wenju Qin, Tianyu You, Lixin Lu, Funian Sun, Chaoyang |
author_sort | Liu, Chen |
collection | PubMed |
description | BACKGROUND: Ovarian cancer (OC) is one of the most lethal gynecologic cancers. Growing evidence has proven that CDK4/6 plays a key role in tumor immunity and the prognosis of many cancers. However, the expression and function of CDK4/6 in OC remain unclear. Therefore, we aimed to explore the influence of CDK4/6 in OC, especially on immunity. METHODS: We analyzed CDK4/6 expression and prognosis using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Genotype Tissue Expression (GTEx) data. Subsequently, we used the cytoHubba plug-in of Cytoscape software and starBase to identify the noncoding RNAs (ncRNAs) regulating CDK4/6. Finally, we verified the effect of CDK4/6 on immunity in OC cell lines and animal models. RESULTS: CDK4/6 expression was higher in OC tissues than in normal ovarian tissues, and the high expression levels of CDK4/6 contributed to the immunosuppressive state of OC and were thus related to the poor prognosis of OC patients. This was also in general agreement with the results of OC cell line and animal experiments. Mechanistically, the CDK4/6 inhibitor palbociclib increased the secretion of interferon (IFN)-γ and the interferon-stimulated gene (ISG) response, thereby upregulating the expression of antigen-presenting molecules; this effect was partly dependent on the STING pathway and thus activated immunity in OC. Additionally, according to public data, the LRRC75A-AS1-hsa-miR-330-5p axis could inhibit the immune response of OC patients by upregulating CDK4/6, leading to a poor prognosis. CONCLUSION: CDK4/6 affects the immune microenvironment of OC and correlates with the prognosis of OC patients. |
format | Online Article Text |
id | pubmed-8795791 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87957912022-01-29 The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer Liu, Chen Huang, Yuhan Cui, Yaoyuan Zhou, Jun Qin, Xu Zhang, Li Li, Xi Li, Yuan Guo, Ensong Yang, Bin Li, Xi Fan, Junpeng Li, Xiong Fu, Yu Liu, Si Hu, Dianxing Xiao, Rourou Wang, Zizhuo Dou, Yingyu Wang, Wei Li, Wenting Yang, Xiaohang Liu, Jingbo Peng, Wenju Qin, Tianyu You, Lixin Lu, Funian Sun, Chaoyang Front Immunol Immunology BACKGROUND: Ovarian cancer (OC) is one of the most lethal gynecologic cancers. Growing evidence has proven that CDK4/6 plays a key role in tumor immunity and the prognosis of many cancers. However, the expression and function of CDK4/6 in OC remain unclear. Therefore, we aimed to explore the influence of CDK4/6 in OC, especially on immunity. METHODS: We analyzed CDK4/6 expression and prognosis using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Genotype Tissue Expression (GTEx) data. Subsequently, we used the cytoHubba plug-in of Cytoscape software and starBase to identify the noncoding RNAs (ncRNAs) regulating CDK4/6. Finally, we verified the effect of CDK4/6 on immunity in OC cell lines and animal models. RESULTS: CDK4/6 expression was higher in OC tissues than in normal ovarian tissues, and the high expression levels of CDK4/6 contributed to the immunosuppressive state of OC and were thus related to the poor prognosis of OC patients. This was also in general agreement with the results of OC cell line and animal experiments. Mechanistically, the CDK4/6 inhibitor palbociclib increased the secretion of interferon (IFN)-γ and the interferon-stimulated gene (ISG) response, thereby upregulating the expression of antigen-presenting molecules; this effect was partly dependent on the STING pathway and thus activated immunity in OC. Additionally, according to public data, the LRRC75A-AS1-hsa-miR-330-5p axis could inhibit the immune response of OC patients by upregulating CDK4/6, leading to a poor prognosis. CONCLUSION: CDK4/6 affects the immune microenvironment of OC and correlates with the prognosis of OC patients. Frontiers Media S.A. 2022-01-14 /pmc/articles/PMC8795791/ /pubmed/35095879 http://dx.doi.org/10.3389/fimmu.2021.799171 Text en Copyright © 2022 Liu, Huang, Cui, Zhou, Qin, Zhang, Li, Li, Guo, Yang, Li, Fan, Li, Fu, Liu, Hu, Xiao, Wang, Dou, Wang, Li, Yang, Liu, Peng, Qin, You, Lu and Sun https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Liu, Chen Huang, Yuhan Cui, Yaoyuan Zhou, Jun Qin, Xu Zhang, Li Li, Xi Li, Yuan Guo, Ensong Yang, Bin Li, Xi Fan, Junpeng Li, Xiong Fu, Yu Liu, Si Hu, Dianxing Xiao, Rourou Wang, Zizhuo Dou, Yingyu Wang, Wei Li, Wenting Yang, Xiaohang Liu, Jingbo Peng, Wenju Qin, Tianyu You, Lixin Lu, Funian Sun, Chaoyang The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer |
title | The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer |
title_full | The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer |
title_fullStr | The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer |
title_full_unstemmed | The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer |
title_short | The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer |
title_sort | immunological role of cdk4/6 and potential mechanism exploration in ovarian cancer |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795791/ https://www.ncbi.nlm.nih.gov/pubmed/35095879 http://dx.doi.org/10.3389/fimmu.2021.799171 |
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