CDK1 serves as a novel therapeutic target for endometrioid endometrial cancer

Ying, Xue; Che, Xuan; Wang, Jianzhang; Zou, Gen; Qin, Yu; Zhang, Xinmei

doi:10.7150/jca.51139

Cited by 29 publications

(21 citation statements)

References 54 publications

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“…CDKs are critical for controlling all aspects of cell division and modulating transcription in response to several extracellular and intracellular cues [12,13]. CDK1, with a molecular weight of 34 kD, is encoded by cell division cycle gene 2 and is a member of the Ser/Thr protein kinase family [14]. As the rst CDK to be identi ed, CDK1 is conserved in all organisms, playing important roles in mitosis and driving cells into the S phase in the absence of CDK2 [12].…”

Section: Discussionmentioning

confidence: 99%

GPRIN1 promotes gallbladder cancer progression through the CDK1 pathway

Shen

et al. 2022

Preprint

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Purpose Recent studies have shown that G protein-regulated inducer of neurite outgrowth 1 (GPRIN1) regulates cancer proliferation and migration. However, there is limited research regarding its role in gallbladder cancer (GBC). We aimed to investigate the mechanism by which GPRIN1 promotes GBC cell proliferation and migration. Methods Immunohistochemistry was performed to visualize in situ GPRIN1 expression in 65 human GBC tissues and 59 corresponding normal tissues. The Kaplan–Meier method was used to analyze the correlation between GPRIN1 and overall survival. Cell proliferation (Celigo and MTT), apoptosis (FACS), and cell migration and invasion assays and a subcutaneous xenograft tumor model were used to define the effects of GPRIN1 downregulation in GBC cells in vitro and in vivo. Coimmunoprecipitation assays, mass spectrometry and Western blotting were performed to identify GPRIN1-interacting proteins. Cell proliferation, MTT and Transwell assays were performed to verify the functional recovery effect of cyclin-dependent protein kinase 1 (CDK1) on GPRIN1. Proteomic analysis of differentially expressed proteins and/or phosphorylated peptides was performed. Results GPRIN1 is upregulated in GBC tumor tissues and high GPRIN1 expression is positively correlated with a poor prognosis in GBC patients. High GPRIN1 expression reinforced the proliferative and invasive capacities of GBC in vitro and in vivo. Coimmunoprecipitation assays, mass spectrometry and Western blotting validated the direct interaction between GPRIN1 and CDK1. Cell proliferation, MTT and Transwell assays suggested that CDK1 exerts a functional recovery effect on GPRIN1. Proteomic analysis revealed the involvement of CDK1 in many biological processes and cellular pathways. Conclusions GPRIN1 promotes the invasion and metastasis of GBC cells via CDK1 pathway activation.

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Section: Discussionmentioning

confidence: 99%

GPRIN1 promotes gallbladder cancer progression through the CDK1 pathway

Shen

et al. 2022

Preprint

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“…CDK1 (Cyclin-dependent kinase 1) plays a critical role in eukaryotic cell cycle control by regulating centrosome cycling and mitotic initiation. There is growing evidence found that CDK1 can be used as a potential biomarker for a variety of diseases, such as Rhabdomyosarcoma [49], endometrioid endometrial cancer [50]. Furthermore, in recent studies, CDK1, promotes the phosphorylation of RAPTOR during mitosis, leading to mTORC1 phosphorylation and affecting the autophagic process [51], which plays an important role in cardiac diseases as a degradation process of cellular self, especially in myocarditis or cardiomyopathy [52].…”

Section: Plos Onementioning

confidence: 99%

Identification of critical genes and molecular pathways in COVID-19 myocarditis and constructing gene regulatory networks by bioinformatic analysis

Zhang

et al. 2022

PLoS ONE

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Background There is growing evidence of a strong relationship between COVID-19 and myocarditis. However, there are few bioinformatics-based analyses of critical genes and the mechanisms related to COVID-19 Myocarditis. This study aimed to identify critical genes related to COVID-19 Myocarditis by bioinformatic methods, explore the biological mechanisms and gene regulatory networks, and probe related drugs. Methods The gene expression data of GSE150392 and GSE167028 were obtained from the Gene Expression Omnibus (GEO), including cardiomyocytes derived from human induced pluripotent stem cells infected with SARS-CoV-2 in vitro and GSE150392 from patients with myocarditis infected with SARS-CoV-2 and the GSE167028 gene expression dataset. Differentially expressed genes (DEGs) (adjusted P-Value <0.01 and |Log2 Fold Change| ≥2) in GSE150392 were assessed by NetworkAnalyst 3.0. Meanwhile, significant modular genes in GSE167028 were identified by weighted gene correlation network analysis (WGCNA) and overlapped with DEGs to obtain common genes. Functional enrichment analyses were performed by using the "clusterProfiler" package in the R software, and protein-protein interaction (PPI) networks were constructed on the STRING website (https://cn.string-db.org/). Critical genes were identified by the CytoHubba plugin of Cytoscape by 5 algorithms. Transcription factor-gene (TF-gene) and Transcription factor-microRibonucleic acid (TF-miRNA) coregulatory networks construction were performed by NetworkAnalyst 3.0 and displayed in Cytoscape. Finally, Drug Signatures Database (DSigDB) was used to probe drugs associated with COVID-19 Myocarditis. Results Totally 850 DEGs (including 449 up-regulated and 401 down-regulated genes) and 159 significant genes in turquoise modules were identified from GSE150392 and GSE167028, respectively. Functional enrichment analysis indicated that common genes were mainly enriched in biological processes such as cell cycle and ubiquitin-protein hydrolysis. 6 genes (CDK1, KIF20A, PBK, KIF2C, CDC20, UBE2C) were identified as critical genes. TF-gene interactions and TF-miRNA coregulatory network were constructed successfully. A total of 10 drugs, (such as Etoposide, Methotrexate, Troglitazone, etc) were considered as target drugs for COVID-19 Myocarditis. Conclusions Through bioinformatics method analysis, this study provides a new perspective to explore the pathogenesis, gene regulatory networks and provide drug compounds as a reference for COVID-19 Myocarditis. It is worth highlighting that critical genes (CDK1, KIF20A, PBK, KIF2C, CDC20, UBE2C) may be potential biomarkers and treatment targets of COVID-19 Myocarditis for future study.

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“…CDK1 has been found as one of the most important therapeutic drug targets for Endometrial Cancer (EC) which is one of the most life threatening and devastating tumors. Its level is highly increased in endometrial cancer so this is regarded as essential target in future as it arrest G2/M phase of cell cycle leading to apoptosis and activates DNA repair homologous recombination pathway [19]. RO-3306 is one of the CDK1 inhibitors which induces cell cycle arrest at G2 stage.…”

Section: Cyclin Dependent Kinases (Cdks)mentioning

confidence: 99%

Emerging Therapeutic Role of CDK Inhibitors in Targeting Cancer Stem Cells

Parveen¹,

Ashfaq²,

Shahid³

et al. 2021

J Biomed Res Environ Sci

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Within a tumor, Cancer Stem Cells (CSCs) exists and own similar characteristics of a normal stem cell thus contributing towards aggressiveness of cancer by playing crucial role in tumor recurrence and metastasis capability. Various studies have been conducted to therapeutically target CSCs. One of the approaches include is to inhibit cell cycle progression in CSCs. Within last two decades cell cycle and role of various components in its regulation is firmly established. Cell cycle is regulated by Cyclin Dependent Kinases (CDK) bound to cyclin. CDK activity can be blocked by Cyclin-Dependent Kinase Inhibitors (CKIs) which can either bind cyclin/CDK complex or CDK alone and thus stops cell cycle. In this review various studies are discussed that have investigated the therapeutic role of CKIs in eradicating CSCs by inhibiting cell cycle. Overall, the analysis suggests that CKIs could be a potential therapeutic option in controlling CSCs populating in a tumor.

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CDK1 serves as a novel therapeutic target for endometrioid endometrial cancer

Cited by 29 publications

References 54 publications

GPRIN1 promotes gallbladder cancer progression through the CDK1 pathway

GPRIN1 promotes gallbladder cancer progression through the CDK1 pathway

Identification of critical genes and molecular pathways in COVID-19 myocarditis and constructing gene regulatory networks by bioinformatic analysis

Emerging Therapeutic Role of CDK Inhibitors in Targeting Cancer Stem Cells

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