Inhibition of Cyclin-Dependent Kinase 8/Cyclin-Dependent Kinase 19 Suppresses Its Pro-Oncogenic Effects in Prostate Cancer

Offermann, Anne; Joerg, Vincent; Becker, Finn; Roesch, Marie C.; Kang, Duan; Lemster, Anna-Lena; Behrends, Jochen; Merseburger, Axel S.; Čulig, Zoran; Sailer, Verena; Brägelmann, Johannes; Kirfel, Jutta; Perner, Sven

doi:10.1016/j.ajpath.2022.01.010

Cited by 8 publications

(10 citation statements)

References 29 publications

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“…CDK8 is a transcription factor and has a pro-tumor role in diverse human cancers, and is thus considered a potential drug target for cancer therapy ( 44 ). Research has shown that CDK8 and CDK19 are highly expressed in prostate cancer, and their inhibitors can curb the metastasis of prostate cancer ( 45 ). In a previous report, a novel CDK8 inhibitor was shown to suppress the metastasis of prostate cancer in vivo and in vitro ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

LncRNA HEIH modulates the proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating the miR-193a-5p/CDK8 axis

Huang,

Li,

et al. 2024

Transl Cancer Res

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Background Hepatocellular carcinoma (HCC), a malignant tumor with a high mortality rate, is a serious problem worldwide. This research sought to examine how long non-coding RNA (lncRNA) high expression in hepatocellular carcinoma ( HEIH ) affects the development and progression of HCC. Methods The expression of HEIH in HCC patients and HCC cell lines was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, HEIH was knocked down, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, wound-healing and transwell assays were conducted to evaluate the effects of HEIH on the proliferation, migration, and invasion of the HCC cells, respectively. A xenografted mice model was constructed to investigate the function of HEIH on HCC tumorigenesis in vivo . The interactions among HEIH , microRNA (miR)-193a-5p and cyclin-dependent kinase 8 ( CDK8 ) were also investigated by dual luciferase reporter (DLR) gene and RNA immunoprecipitation (RIP) assays. Results HEIH was highly expressed in HCC tissues, and was correlated with advanced TNM stage and the absence of vascular invasion. The in vitro experiments showed that silencing HEIH restrained the viability, migration, and invasion of HCC cells, and hampered xenograft tumor growth in vivo . Additionally, HEIH was shown to bind directly to microRNA 193a-5p ( miR-193a-5p ) and facilitate the expression of the target gene CDK8 in the HCC cells. CDK8 overexpression and miR-193a-5p silencing attenuated the effects of si- HEIH -induced inhibition on the proliferation, migration, and invasion of HCC cells. Conclusions Silencing HEIH restrained the proliferation, migration, and invasion of HCC cells via the miR-193a-5p / CDK8 axis.

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Section: Discussionmentioning

confidence: 99%

LncRNA HEIH modulates the proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating the miR-193a-5p/CDK8 axis

Huang,

Li,

et al. 2024

Transl Cancer Res

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“…31,32 Inhibition of CDK8/CDK19 as cell cycle-promoting proteins shows a synergistic effect on making androgenindependent LNCaP Abl cells sensitized to bicalutamide when simultaneously applied with antiandrogen drugs, and the reason for this can be a decrease in migration capacity, which probably roots in integrin adhesion. 33 Being sensitive to alterations in migration capabilities helps inhibit EMT regulators such as SNAI2 that reduces the malignant properties of the tumor, resulting in drug response. Cytoskeleton components play a key role in the coordination and necessary adjustments for the EMT process.…”

Section: ■ the Role Of Cell Membrane And Cytoskeleton Proteins In Bic...mentioning

confidence: 99%

Updates on Overcoming Bicalutamide Resistance: A Glimpse into Resistance to a Novel Antiandrogen

Izady,

Khatami,

Ahadi

et al. 2024

ACS Pharmacol. Transl. Sci.

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The standard androgen deprivation therapy for advanced prostate cancer includes the use of bicalutamide, which is a well-known antagonist of androgen receptors. Despite numerous benefits of the drugs in prostate cancer treatment, there is always a risk of developing a resistant phenotype, which paves the way for a more aggressive and low-survival type of prostate cancer. Over the years, many studies have investigated the candidate mechanisms of such resistance and have managed to find possible therapeutic solutions. In this Review, we shed light on the heterogeneous dynamics of progression to resistance against bicalutamide treatment, referring to the most recent studies and the approaches that have been so far discussed. This Review tries to offer a deep and comprehensive understanding about how the resistant cells become sensitive to the drug and what corresponding pathways lead to an appropriate solution for the antiandrogen resistance challenge.

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“…CDK8 is amplified in colon cancer, pancreatic cancer, and other cancer ( Firestein et al, 2008 ; Offermann et al, 2022 ). The proliferation of colon cancer cells that overexpress CDK8 can be effectively inhibited by knocking down CDK8, as reported in previous studies.…”

Section: Emerging Roles Of Cdk8 In Tumorigenesismentioning

confidence: 99%

“…The CDK8 protein kinase, consisting of 464 amino acids, frequently exhibits amplification in colorectal cancer ( Firestein et al, 2008 ; He et al, 2011 ). Moreover, the involvement of CDK8 in the pathogenesis of gastric cancer, breast cancer, prostate cancer, melanoma, and acute myeloid leukemia highlights its potential as a promising therapeutic target for various malignancies ( Kapoor et al, 2010 ; Broude et al, 2015 ; Nitulescu et al, 2017 ; Offermann et al, 2022 ; Xu et al, 2023 ). However, CDK8 exerts an anticancer role in endometrial cancer in addition to its role in tumor growth, implying that CDK8 has a different function in the growth of cancer ( Gu et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Unveiling the impact of CDK8 on tumor progression: mechanisms and therapeutic strategies

Yin,

He,

Chen

et al. 2024

Front. Pharmacol.

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CDK8 is an important member of the cyclin-dependent kinase family associated with transcription and acts as a key “molecular switch” in the Mediator complex. CDK8 regulates gene expression by phosphorylating transcription factors and can control the transcription process through Mediator complex. Previous studies confirmed that CDK8 is an important oncogenic factor, making it a potential tumor biomarker and a promising target for tumor therapy. However, CDK8 has also been confirmed to be a tumor suppressor, indicating that it not only promotes the development of tumors but may also be involved in tumor suppression. Therefore, the dual role of CDK8 in the process of tumor development is worth further exploration and summary. This comprehensive review delves into the intricate involvement of CDK8 in transcription-related processes, as well as its role in signaling pathways related to tumorigenesis, with a focus on its critical part in driving cancer progression.

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Inhibition of Cyclin-Dependent Kinase 8/Cyclin-Dependent Kinase 19 Suppresses Its Pro-Oncogenic Effects in Prostate Cancer

Cited by 8 publications

References 29 publications

LncRNA HEIH modulates the proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating the miR-193a-5p/CDK8 axis

LncRNA HEIH modulates the proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating the miR-193a-5p/CDK8 axis

Updates on Overcoming Bicalutamide Resistance: A Glimpse into Resistance to a Novel Antiandrogen

Unveiling the impact of CDK8 on tumor progression: mechanisms and therapeutic strategies

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