A comprehensive bioinformatic analysis of cyclin-dependent kinase 2 (CDK2) in glioma

Liu, Hengrui; Weng, Jieling

doi:10.1016/j.gene.2022.146325

Cited by 22 publications

(11 citation statements)

References 37 publications

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“…In addition, we further analyzed the expression level of these target genes in LIHC paired samples from TCGA data. Cancer and noncancer data from the same patients were compared and analyzed by paired t -test [ 35 – 36 ]. Results showed that GABRA3, SLC6A3, GABRQ, SCN4A, and GABRG3 were overexpressed in cancer compared with normal liver tissues ( Figure 4(c) ).…”

Section: Resultsmentioning

confidence: 99%

Screening and Validation of a Carvacrol-Targeting Viability-Regulating Protein, SLC6A3, in Liver Hepatocellular Carcinoma

Yin

Chen

et al. 2022

Disease Markers

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Background. Liver hepatocellular carcinoma (LIHC) is the second leading cause of tumor-related death in the world. Carvacrol was also found to inhibit multiple cancer types. Here, we proposed that Carvacrol inhibited LIHC. Methods. We used MTT assay to determine the inhibition of Carvacrol on LIHC cells. BATMAN-TCM was used to predict targets of Carvacrol. These targets were further screened by their survival association and expression in cancer using TCGA data. The bioinformatic screened candidates were further validated in in vitro experiments and clinical samples. Finally, docking models of the interaction of Carvacrol and target protein were conducted. Results. Carvacrol inhibited the viability of LIHC cell lines. 40 target genes of Carvacrol were predicted, 8 of them associated with survival. 4 genes were found differentially expressed in LIHC vs. normal liver. Among these genes, the expression of SLC6A3 and SCN4A was found affected by Carvacrol in LIHC cells, but only SLC6A3 correlated with the viability inhibition of Carvacrol on LIHC cell lines. A docking model of the interaction of Carvacrol and SLC6A3 was established with a good binding affinity. SLC6A3 knockdown and expression revealed that SLC6A3 promoted the viability of LIHC cells. Conclusion. Carvacrol inhibited the viability of LIHC cells by downregulating SLC6A3.

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Section: Resultsmentioning

confidence: 99%

Screening and Validation of a Carvacrol-Targeting Viability-Regulating Protein, SLC6A3, in Liver Hepatocellular Carcinoma

Yin

Chen

et al. 2022

Disease Markers

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“…[ 39 ] A low CDK2 expression is associated with how genes regulate normal brain functions while a high CDK2 expression is associated with how genes regulate immune system cells and cancer. [ 40 ] CDK7 has been shown to play important roles in malignancy pathogenesis. The promotion of apoptosis is accompanied by the blocking of CDK7‐dependent transcriptional addiction [ 41 ] .…”

Section: Discussionmentioning

confidence: 99%

Lily Polysaccharide Nano‐Selenium Promotes A549 Cells Apoptosis through Cell Cycle Inhibition

Wei,

Wang,

Hua

et al. 2024

Starch Stärke

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This study uses Lilium davidii var. unicolor (Lanzhou lily) polysaccharides extracted from bulbs to prepare nano‐selenium (nano‐Se) polysaccharide (LPS). Here, the study explores the molecular structure characterization, inhibition effects, and mechanisms of action of prepared LPS on A549 lung cancer cells. The LPS structure is characterized using Fourier‐transform infrared spectroscopy (FTIR), UV spectroscopy (UV–vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), X‐ray photoelectron spectroscopy (XPS), etc. Results show that selenized polysaccharides bonded through electrostatic adsorption, with an average LPS particle size of 243.75 nm and zeta potential of −38.3 mV, which can be stably preserved at 4 °C for more than 3 months. The in vitro antitumor activity experiment shows that the prepared LPS inhibited A549 cell proliferation while affecting cell migration. Cell cycle analysis shows that apoptosis is promoted by blocking the G1 phase, while during the late apoptosis stage cells accounted for 60%. RNA‐Seq data analysis shows that the main mechanisms of action on A549 cells are to inhibit DNA replication initiation genes, block the cell cycle, and regulate the expression of apoptosis‐related genes and proteins in promoting cell apoptosis.

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“…First, our phosphoproteomic data indicates that EMP3 KO leads to the inactivation of the cyclin-dependent kinase CDK2. CDK2, which is often upregulated in GBMs compared to normal brain tissue [ 38 ], has been shown to be downstream EGFR target in glioblastoma cell lines [ 8 ]. Its transient activation by AKT is known to be a critical step in the induction of cell cycle progression [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

EMP3 sustains oncogenic EGFR/CDK2 signaling by restricting receptor degradation in glioblastoma

Martija,

Krauß,

Bächle

et al. 2023

acta neuropathol commun

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Epithelial membrane protein 3 (EMP3) is an N-glycosylated tetraspanin with a putative trafficking function. It is highly expressed in isocitrate dehydrogenase-wild-type glioblastoma (IDH-wt GBM), and its high expression correlates with poor survival. However, the exact trafficking role of EMP3 and how it promotes oncogenic signaling in GBM remain unclear. Here, we show that EMP3 promotes EGFR/CDK2 signaling by regulating the trafficking and enhancing the stability of EGFR. BioID2-based proximity labeling revealed that EMP3 interacts with endocytic proteins involved in the vesicular transport of EGFR. EMP3 knockout (KO) enhances epidermal growth factor (EGF)-induced shuttling of EGFR into RAB7 + late endosomes, thereby promoting EGFR degradation. Increased EGFR degradation is rescued by the RAB7 negative regulator and novel EMP3 interactor TBC1D5. Phosphoproteomic and transcriptomic analyses further showed that EMP3 KO converges into the inhibition of the cyclin-dependent kinase CDK2 and the repression of EGFR-dependent and cell cycle transcriptional programs. Phenotypically, EMP3 KO cells exhibit reduced proliferation rates, blunted mitogenic response to EGF, and increased sensitivity to the pan-kinase inhibitor staurosporine and the EGFR inhibitor osimertinib. Furthermore, EGFR-dependent patient-derived glioblastoma stem cells display a transcriptomic signature consistent with reduced CDK2 activity, as well as increased susceptibility to CDK2 inhibition upon EMP3 knockdown. Lastly, using TCGA data, we showed that GBM tumors with high EMP3 expression have increased total and phosphorylated EGFR levels. Collectively, our findings demonstrate a novel EMP3-dependent mechanism by which EGFR/CDK2 activity is sustained in GBM. Consequently, EMP3’s stabilizing effect provides an additional layer of tumor cell resistance against targeted kinase inhibition.

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A comprehensive bioinformatic analysis of cyclin-dependent kinase 2 (CDK2) in glioma

Cited by 22 publications

References 37 publications

Screening and Validation of a Carvacrol-Targeting Viability-Regulating Protein, SLC6A3, in Liver Hepatocellular Carcinoma

Screening and Validation of a Carvacrol-Targeting Viability-Regulating Protein, SLC6A3, in Liver Hepatocellular Carcinoma

Lily Polysaccharide Nano‐Selenium Promotes A549 Cells Apoptosis through Cell Cycle Inhibition

EMP3 sustains oncogenic EGFR/CDK2 signaling by restricting receptor degradation in glioblastoma

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