The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer

Chen Liu; Yuhan Huang; Yuhan Huang; Yaoyuan Cui; Jun Zhou; Xu Qin; Li Zhang; Xi Li; Yuan Li; Ensong Guo; Bin Yang; Xi Li; Junpeng Fan; Xiong Li; Yu Fu; Si Liu; Dianxing Hu; Rourou Xiao; Zizhuo Wang; Yingyu Dou; Wei Wang; Wenting Li; Xiaohang Yang; Jingbo Liu; Wenju Peng; Tianyu Qin; Lixin You; Funian Lu; Chaoyang Sun

doi:10.3389/fimmu.2021.799171

Frontiers in Immunology (Jan 2022)

The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer

Chen Liu,
Yuhan Huang,
Yuhan Huang,
Yaoyuan Cui,
Jun Zhou,
Xu Qin,
Li Zhang,
Xi Li,
Yuan Li,
Ensong Guo,
Bin Yang,
Xi Li,
Junpeng Fan,
Xiong Li,
Yu Fu,
Si Liu,
Dianxing Hu,
Rourou Xiao,
Zizhuo Wang,
Yingyu Dou,
Wei Wang,
Wenting Li,
Xiaohang Yang,
Jingbo Liu,
Wenju Peng,
Tianyu Qin,
Lixin You,
Funian Lu,
Chaoyang Sun

Affiliations

Chen Liu: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Yuhan Huang: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Yuhan Huang: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yaoyuan Cui: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Jun Zhou: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Xu Qin: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Li Zhang: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Xi Li: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yuan Li: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Ensong Guo: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Bin Yang: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Xi Li: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Junpeng Fan: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Xiong Li: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Yu Fu: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Si Liu: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Dianxing Hu: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Rourou Xiao: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Zizhuo Wang: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Yingyu Dou: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Wei Wang: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Wenting Li: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Xiaohang Yang: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Jingbo Liu: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Wenju Peng: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Tianyu Qin: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Lixin You: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Funian Lu: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Chaoyang Sun: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

DOI: https://doi.org/10.3389/fimmu.2021.799171
Journal volume & issue: Vol. 12

Abstract

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BackgroundOvarian 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.MethodsWe 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.ResultsCDK4/6 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.ConclusionCDK4/6 affects the immune microenvironment of OC and correlates with the prognosis of OC patients.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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