CDK12 Promotes Cervical Cancer Progression through Enhancing Macrophage Infiltration

Cervical cancer (CC) is a commonly diagnosed and primary consideration of cancer patient death in female reproductive system malignancy. Cyclin-dependent kinase 12 (CDK12), as a transcription-associated CDK, plays important roles in tumor-promoting behaviors, whereas the underlying mechanisms of CDK...

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Main Authors: Bikang Yang, Jing Chen, Yincheng Teng
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2021/6645885
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author Bikang Yang
Jing Chen
Yincheng Teng
author_facet Bikang Yang
Jing Chen
Yincheng Teng
author_sort Bikang Yang
collection DOAJ
description Cervical cancer (CC) is a commonly diagnosed and primary consideration of cancer patient death in female reproductive system malignancy. Cyclin-dependent kinase 12 (CDK12), as a transcription-associated CDK, plays important roles in tumor-promoting behaviors, whereas the underlying mechanisms of CDK12 in CC progression are still obscure. In this report, we investigated the role of CDK12 in cervical cancer. The current study identified CDK12 mRNA and protein expression remarkably upregulated in CC patients. Upregulated CDK12 was closely associated with CC progression and poor prognosis. In vitro and in vivo functional experiments showed that knockdown of CDK12 inhibited cancer cell proliferation and colony formation and promoted apoptosis. Further investigations demonstrated that CDK12 regulated the immune microenvironment to facilitate the progression of CC cells by promoting macrophage infiltration. Meanwhile, we first demonstrated that nuclear import of CDK12 is mediated by TNPO1 and might be a new therapeutic target in oncology. Collectively, this study pointed out the potential of CDK12 to serve as a novel therapeutic target in restricting CC proliferation and cell cycle process through promoting macrophage infiltration.
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publishDate 2021-01-01
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series Journal of Immunology Research
spelling doaj-art-9ccc037941d44a02a9d32d9fdbcb87e22025-08-20T02:20:19ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/66458856645885CDK12 Promotes Cervical Cancer Progression through Enhancing Macrophage InfiltrationBikang Yang0Jing Chen1Yincheng Teng2Department of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, ChinaDepartment of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, ChinaDepartment of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, ChinaCervical cancer (CC) is a commonly diagnosed and primary consideration of cancer patient death in female reproductive system malignancy. Cyclin-dependent kinase 12 (CDK12), as a transcription-associated CDK, plays important roles in tumor-promoting behaviors, whereas the underlying mechanisms of CDK12 in CC progression are still obscure. In this report, we investigated the role of CDK12 in cervical cancer. The current study identified CDK12 mRNA and protein expression remarkably upregulated in CC patients. Upregulated CDK12 was closely associated with CC progression and poor prognosis. In vitro and in vivo functional experiments showed that knockdown of CDK12 inhibited cancer cell proliferation and colony formation and promoted apoptosis. Further investigations demonstrated that CDK12 regulated the immune microenvironment to facilitate the progression of CC cells by promoting macrophage infiltration. Meanwhile, we first demonstrated that nuclear import of CDK12 is mediated by TNPO1 and might be a new therapeutic target in oncology. Collectively, this study pointed out the potential of CDK12 to serve as a novel therapeutic target in restricting CC proliferation and cell cycle process through promoting macrophage infiltration.http://dx.doi.org/10.1155/2021/6645885
spellingShingle Bikang Yang
Jing Chen
Yincheng Teng
CDK12 Promotes Cervical Cancer Progression through Enhancing Macrophage Infiltration
Journal of Immunology Research
title CDK12 Promotes Cervical Cancer Progression through Enhancing Macrophage Infiltration
title_full CDK12 Promotes Cervical Cancer Progression through Enhancing Macrophage Infiltration
title_fullStr CDK12 Promotes Cervical Cancer Progression through Enhancing Macrophage Infiltration
title_full_unstemmed CDK12 Promotes Cervical Cancer Progression through Enhancing Macrophage Infiltration
title_short CDK12 Promotes Cervical Cancer Progression through Enhancing Macrophage Infiltration
title_sort cdk12 promotes cervical cancer progression through enhancing macrophage infiltration
url http://dx.doi.org/10.1155/2021/6645885
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AT jingchen cdk12promotescervicalcancerprogressionthroughenhancingmacrophageinfiltration
AT yinchengteng cdk12promotescervicalcancerprogressionthroughenhancingmacrophageinfiltration