Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cell cycle dysregulation with overexpression of KIF2C/MCAK is a critical event in nasopharyngeal carcinoma

ABSTRACT: Purpose: Nasopharyngeal carcinoma (NPC) is a common malignant carcinoma of the head and neck, and the biological mechanisms underlying the pathogenesis of NPC remain not fully understood.Thus, more studies are needed to identify novel critical molecular events and key hub genes to develop novel diagnostic and therapeutic strategies for the management and treatment of NPC. Methods: In the present study, we systematically analyzed four independent NPC transcriptomic da-tasets and focused on identifying the critical molecular networks and novel key hub genes implicated in NPC. We found totally 170 common overlapping differentially expressed genes (DEGs) in the four NPC datasets. GO and KEGG pathway analysis revealed that cell cycle dysregulation is a critical event in NPC. Protein-protein interaction (PPI) network analysis identified a 15 hub-gene core network with overexpressed kinesin family member 2C (KIF2C) as a central regulator. Results: Loss-of-function study demonstrated that knockdown of KIF2C significantly inhibited cell growth and cell motility, and delayed cell cycle progression, accompanied with dramatic mitotic defects in spindle formation in NPC cells. RNA-seq analysis revealed that KIF2C knockdown led to deregulation of various downstream genes. KIF2C could also regulate the AKT/mTOR pathways, and enhance paclitaxel sensitivity in NPC cells. Conclusions: Taken together, our results suggest that cell cycle dysregulation is a critical event during NPC pathogenesis and KIF2C is a novel key mitotic hub gene with therapeutic potential in NPC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE176471 | GEO | 2021/06/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Cell cycle dysregulation with overexpression of KIF2C/MCAK is a critical event in nasopharyngeal carcinoma

Project description:Cell cycle dysregulation with overexpression of KIF2C/MCAK is a critical event in nasopharyngeal carcinoma

| PRJNA736377 | ENA

EZH2-mediated H3K27me3 targets transcriptional circuits of neuronal differentiation ChIP-seq

Project description:Our work describes novel roles for EZH2 in the specification of cortical neurons. Previous reports established the current model of EZH2-mediated control of neuronal progenitors differentiation through the regulation of their proliferation and developmental transitions. We built on these findings and studied the role of EZH2 in post-mitotic glutamatergic neurons differentiated from embryonic stem cells, a particularly relevant cell type where the impact of its regulation has thus far remained elusive. Briefly, our key results can be summarized as follows: 1. The conditional deletion of EZH2 at the moment of cell cycle exit in neural progenitors allowed us to study the role of EZH2 selectively in post-mitotic glutamatergic neurons. 2. Time course transcriptomic and epigenomic analyses of H3K27me3 in absence of EZH2 revealed a significant dysregulation of transcriptional networks affecting synaptic plasticity, in particular long term depression. 3. These analyses also revealed potential novel roles of EZH2 in controlling the regulation between the glutamatergic signature and the GABAergic one, suggesting a mechanism entailing failure of Prdm13 repression, a histone methyltransferase with a known role in determining GABAergic neurons specification.

2022-03-28 | E-MTAB-11363 | biostudies-arrayexpress

EZH2-mediated H3K27me3 targets transcriptional circuits of neuronal differentiation

2022-04-18 | E-MTAB-11387 | biostudies-arrayexpress

Nuclear pore complex evolution: A trypanosome Mlp analog functions in chromosomal segregation but lacks transcriptional barrier activity

Project description:The nuclear pore complex (NPC) has dual roles in nucleocytoplasmic transport and chromatin organisation. In many eukaryotes the coiled coil Mlp/Tpr proteins of the NPC nuclear basket have specific roles in interactions with chromatin and defining specialised regions of active transcription, while Mlp2 associates with the mitotic spindle in a cell-cycle dependent manner. We previously identified two putative Mlp-related proteins in African trypanosomes, TbNup110 and TbNup92, the latter of which associates with the spindle. We now provide evidence for independent ancestry for TbNup92/TbNup110 and Mlp/Tpr proteins. However, TbNup92 is required for correct chromosome segregation, with knockout cells exhibiting microaneuploidy and low fidelity telomere segregation. Further, TbNup92 is intimately associated with the mitotic spindle and spindle anchor site, but apparently has minimal roles in the control of gene transcription, indicating that TbNup92 lacks major barrier activity. TbNup92 therefore acts as a functional analog of Mlp/Tpr proteins, and together with the lamina analog NUP-1, represents a cohort of novel proteins operating at the nuclear periphery of trypanosomes, uncovering complex evolutionary trajectories for the NPC and nuclear lamina. Whole transcriptome comparison between parental and TbNup92? cells

2014-04-03 | E-GEOD-56436 | biostudies-arrayexpress

Identification of microproteins in Hep3B cells at different cell cycle stages

Project description:Microproteins are generated from small open reading frames (sORFs) and turn out to play various vital biological functions. As an essential biological event of eukaryotic cells, the cell cycle is involved in cell replication and division. For such a highly regulated event, microproteins associated with cell cycle regulation remained unclarified. Utilizing a combination of bottom-up and top-down proteomics, we analyzed microproteins at specific cell cycle stages of Hep3B cells. A total of 657 microproteins were identified under three cell cycle stages, including 151 in the G0/G1 stage, 163 in the S stage, and 132 in the G2/M stage. The annotation of these microproteins showed their cell cycle-specific functions, such as translation, nuclear assembly, chromatin organization, G2/M transition of the mitotic cell cycle. Meanwhile, more than 50 % of identified microproteins were ncRNA encoded. These non-annotated novel microproteins contain several function domains, such as nucleoside diphosphate kinase (NDK) domain, high mobility group (HMG) domain, and DNA-binding domain. That suggested the potential functions of these novel microproteins in specific cell cycle stages. This study presented a large-scale profile of microproteins at different cell cycle stages from Hep3B and may provide new perspectives on the regulation mechanism of the cell cycle.

2021-12-09 | PXD030286 | iProX

Nuclear pore complex evolution: A trypanosome Mlp analog functions in chromosomal segregation but lacks transcriptional barrier activity

2014-04-03 | GSE56436 | GEO

Multi-omic analyses reveal interaction networks linking CIC to cell cycle regulation

Project description:CIC encodes a transcriptional repressor inactivated by loss-of-function mutations in several cancer types, indicating that it may function as a tumor suppressor. Recent data indicate that CIC may regulate cell cycle genes in humans; however, a thorough investigation of this proposed role has not yet been reported. Here, we used single-cell RNA sequencing technology to provide evidence that inactivation of CIC in human cell lines resulted in transcriptional dysregulation of genes involved in cell cycle control. We also mapped CIC’s protein-protein and genetic interaction networks, identifying interactions between CIC and members of the Switch/Sucrose Non-Fermenting (SWI/SNF) complex, as well as novel candidate interactions between CIC and cell cycle regulators. We further showed that CIC loss was associated with an increased frequency of mitotic defects in human cell lines and a mouse model. Overall, our study positions CIC as a cell cycle regulator and indicates that CIC loss can lead to mitotic errors, consistent with CIC’s emerging role as a tumor suppressor of relevance in several cancer contexts.

2023-06-30 | PXD030942 | Pride

Dynamic partitioning of branched-chain amino acids-derived nitrogen supports renal cancer progression

Project description:<p>Metabolic reprogramming is critical for tumor initiation and progression. However, the exact impact of specific metabolic changes on cancer progression is poorly understood. Here, we integrate multimodal analyses of primary and metastatic clonally-related clear cell renal cancer cells (ccRCC) grown in physiological media to identify key stage-specific metabolic vulnerabilities. We show that a VHL loss-dependent reprogramming of branched-chain amino acid catabolism sustains the de novo biosynthesis of aspartate and arginine enabling tumor cells with the flexibility of partitioning the nitrogen of the amino acids depending on their needs. Importantly, we identify the epigenetic reactivation of argininosuccinate synthase (ASS1), a urea cycle enzyme suppressed in primary ccRCC, as a crucial event for metastatic renal cancer cells to acquire the capability to generate arginine, invade in vitro and metastasize in vivo. Overall, our study uncovers a novel mechanism of metabolic flexibility occurring during ccRCC progression, paving the way for the development of novel stage-specific therapies</p>

2022-12-08 | MTBLS5615 | MetaboLights

Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling

Project description:Epstein-Barr virus (EBV) is etiologically linked to infectious mononucleosis and several human cancers. EBV encodes a conserved protein kinase BGLF4 that plays a key role in the viral life cycle. To provide new insight into the host proteins regulated by BGLF4, we utilized SILAC-based quantitative proteomics to compare site-specific phosphorylation in BGLF4-expressing cells and found up-regulated phosphorylation of 3,046 unique sites on 1,328 proteins. Motif analysis of the upregulated phospho-proteins found enrichment in CDK1/BGLF4, ATM, ATR and Aurora kinase substrates while functional analyses revealed significant enrichment of pathways related to the DNA damage response, mitosis and cell cycle plus phosphorylation of nuclear pore proteins. Phosphorylation of proteins associated with the mitotic spindle assembly checkpoint (SAC) indicated checkpoint activation, an event that inactivates the anaphase promoting complex/cyclosome, APC/C. Our data reveal that manipulation of mitotic kinase signaling and SAC activation are mechanisms associated with lytic EBV replication.

2015-12-07 | PXD002411 | Pride