An overview of CDK3 in cancer: clinical significance and pharmacological implications

Teo, Theodosia; Kasirzadeh, Sara; Albrecht, Hugo; Sykes, Matthew J.; Yang, Yuchao; Wang, Shudong

doi:10.1016/j.phrs.2022.106249

Cited by 6 publications

(3 citation statements)

References 115 publications

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“…CDK3 is a significant driver in retinoblastoma (Rb) phosphorylation during the G0/G1 transition of the cell cycle. The expression of CDK3 is deficient in normal tissue but overexpressed in many cancers 50 . In our research, CDK3 was upregulated in OS tissue, and downregulating of CDK3 would inhibit the proliferation and migration capabilities of OS cells.…”

Section: Discussionsupporting

confidence: 45%

“…The expression of CDK3 is deficient in normal tissue but overexpressed in many cancers. 50 In our research, CDK3 was upregulated in OS tissue, and downregulating of CDK3 would inhibit the proliferation and migration capabilities of OS cells. Thus, we speculated that the overexpression of CDK3 in OS might correlate with mechanisms of proliferation and migration.…”

Section: Discussionmentioning

confidence: 55%

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Identification of an EMT‐related gene‐based prognostic signature in osteosarcoma

et al. 2023

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Background The correlation between epithelial‐mesenchymal transition (EMT) and osteosarcoma (OS) has been widely reported. Integration of the EMT‐related genes to predict the prognosis is significant for investigating the mechanism of EMT in OS. Here, we aimed to construct a prognostic EMT‐related gene signature for OS. Methods Transcriptomic and survival data of OS patients were downloaded from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO). We performed univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and stepwise multivariate Cox regression analysis to construct EMT‐related gene signatures. Kaplan–Meier analysis and time‐dependent receiver operating characteristic (ROC) were applied to evaluate its predictive performance. GSVA, ssGSEA, ESTIMATE, and scRNA‐seq were performed to investigate the tumor microenvironment, and the correlation between IC50 of drugs and ERG score was investigated. Furthermore, Edu and transwell experiments were conducted to assess the malignancy of OS cells. Results We constructed a novel EMT‐related gene signature (including CDK3, MYC, UHRF2, STC2, COL5A2, MMD, and EHMT2) for outcome prediction of OS. According to the signature, patients stratified into high‐ and low‐ERG‐score groups exhibited significantly different prognoses. ROC curves and Kaplan–Meier analysis revealed a promising performance of the signature with external validation. GSVA, ssGSEA, ESTIMATE algorithm, and scRNA‐seq excavated EMT‐related pathways and suggested the correlation between ERG score and immune activation. Notably, the pivotal gene CDK3 was upregulated in OS tissue and positively related to OS cell proliferation and migration. Conclusion Our EMT‐related gene signature might reference OS risk stratification and guide clinical strategies as an independent prognostic factor in OS.

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Section: Discussionsupporting

confidence: 45%

Section: Discussionmentioning

confidence: 55%

Identification of an EMT‐related gene‐based prognostic signature in osteosarcoma

et al. 2023

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“…Cyclin A, C, E Promotes G0/G1 and G1/S transitions (Ren & Rollins, 2004;Sage, 2004;Satyanarayana & Kaldis, 2009b;Teo et al, 2022;van den Heuvel & Harlow, 1993;Ye et al, 2001) Targets transcriptional repressor Rb (Hofmann & Livingston, 1996;Ren & Rollins, 2004) Phosphorylates c-Jun and ATF1 to simulate cell transformation (Cho et al, 2009;Zheng et al, 2008) Promotes apoptosis (Meikrantz & Schlegel, 1996) Promotes EMT (Lu et al, 2016) CDK5 p35, p38 Blocks cell cycle in postmitotic neurons (Cicero & Herrup, 2005;Zhang et al, 2008) Promotes proliferation in neuroendocrine thyroid cancer (Pozo et al, 2013) Implicated in transcriptional programs for neuronal differentiation (Cicero & Herrup, 2005) Activates STAT3 (A. K. Y. Fu et al, 2004) Inhibits MEF2 to promote apoptosis (Gong et al, 2003) Activates mSds3 to promote histone acetylation (Z.…”

Section: Cdk3mentioning

confidence: 99%

Cyclin‐dependent kinases: Masters of the eukaryotic universe

Pluta,

Studniarek,

Murphy

et al. 2023

WIREs RNA

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A family of structurally related cyclin‐dependent protein kinases (CDKs) drives many aspects of eukaryotic cell function. Much of the literature in this area has considered individual members of this family to act primarily either as regulators of the cell cycle, the context in which CDKs were first discovered, or as regulators of transcription. Until recently, CDK7 was the only clear example of a CDK that functions in both processes. However, new data points to several “cell‐cycle” CDKs having important roles in transcription and some “transcriptional” CDKs having cell cycle‐related targets. For example, novel functions in transcription have been demonstrated for the archetypal cell cycle regulator CDK1. The increasing evidence of the overlap between these two CDK types suggests that they might play a critical role in coordinating the two processes. Here we review the canonical functions of cell‐cycle and transcriptional CDKs, and provide an update on how these kinases collaborate to perform important cellular functions. We also provide a brief overview of how dysregulation of CDKs contributes to carcinogenesis, and possible treatment avenues.This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes RNA Processing > 3′ End Processing RNA Processing > Splicing Regulation/Alternative Splicing

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