The high overlap between the Rummagene set and the RummaGEO set can be attributed to their shared focus on cell cycle regulation and DNA replication processes, which are central to both endothelial cell cycle progression and cancer cell proliferation.
The RummaGEO gene set, GSE159694-3-vs-0-human up, involves genes that are upregulated in endothelial cells during the late G1 phase compared to untreated endothelial cells derived from human embryonic stem cells (hESCs). This study highlights the role of retinoic acid in promoting an early G1 state, which is crucial for hemogenic endothelial cell specification. The focus on cell cycle phases suggests an emphasis on genes involved in cell cycle regulation and DNA replication.
The Rummagene set, PMC7185143-aging-12-102991-s001..docx-0-Gene_name, is derived from a study investigating the role of KIAA0101 in nasopharyngeal carcinoma (NPC). KIAA0101 is identified as a key regulator of cancer progression, influencing cell proliferation, DNA replication, and cell cycle arrest. The study highlights the overexpression of KIAA0101 in NPC and its regulation through MAP kinase phosphorylation-dependent activation of ELK1, which affects cell cycle and DNA replication processes.
The enriched terms from the overlapping genes further support this connection. Terms such as Cell Cycle WP179 (Library: WikiPathway_2023_Human Rank: 2), DNA Replication WP466 (Library: WikiPathway_2023_Human Rank: 3), and DNA Metabolic Process (GO:0006259) (Library: GO_Biological_Process_2023 Rank: 1) indicate a shared involvement in cell cycle and DNA replication pathways. Additionally, the presence of terms like Retinoblastoma Gene In Cancer WP2446 (Library: WikiPathway_2023_Human Rank: 1) and Chromosomal Instability MP:0008866 (Library: MGI_Mammalian_Phenotype_Level_4_2024 Rank: 1) suggests a link to cancer-related processes, which aligns with the role of KIAA0101 in NPC.
Enriched Terms Visualization:
Overall, the significant overlap between these gene sets can be attributed to their mutual involvement in regulating cell cycle and DNA replication, processes that are critical in both endothelial cell differentiation and cancer cell proliferation.
Hypothesis 1: PMC9762333-ccr-21-3329_supplementary_tables_1-3_supp1-3.docx-1-Proliferation;GSE159694-3-vs-0-human up
The high overlap between the Rummagene set and the RummaGEO set can be attributed to their shared focus on cell proliferation and cell cycle regulation, which are central themes in both studies.
The RummaGEO gene set, GSE159694-3-vs-0-human up, involves genes that are upregulated in endothelial cells during the late G1 phase compared to untreated endothelial cells derived from human embryonic stem cells (hESCs). This study investigates how retinoic acid influences the cell cycle, particularly promoting an early G1 state to facilitate hemogenic endothelial cell specification. The focus on cell cycle phases, particularly the transition from G1 to S phase, is crucial for understanding how endothelial cells prepare for proliferation and differentiation.
On the other hand, the Rummagene set, PMC9762333-ccr-21-3329_supplementary_tables_1-3_supp1-3.docx-1-Proliferation, is derived from a study examining transcriptomic determinants of response to pembrolizumab monotherapy across various solid tumor types. This study evaluates several gene expression signatures, including proliferation, to understand their relationship with the response to pembrolizumab, an immune checkpoint inhibitor. The proliferation signature is hypothesized to have a positive association with treatment response, indicating that cell cycle and proliferation-related genes are critical in determining how tumors respond to therapy.
The enriched terms from the overlapping genes further support this hypothesis. Terms such as Retinoblastoma Gene In Cancer WP2446 (Library: WikiPathway_2023_Human Rank: 1), DNA Replication WP466 (Library: WikiPathway_2023_Human Rank: 2), and Cell Cycle WP179 (Library: WikiPathway_2023_Human Rank: 3) highlight the involvement of cell cycle regulation and DNA replication processes. Additionally, GO Biological Process terms like DNA Metabolic Process (GO:0006259) (Library: GO_Biological_Process_2023 Rank: 1), DNA-templated DNA Replication (GO:0006261) (Library: GO_Biological_Process_2023 Rank: 2), and Mitotic Sister Chromatid Segregation (GO:0000070) (Library: GO_Biological_Process_2023 Rank: 3) emphasize the importance of DNA replication and mitosis, which are fundamental to both endothelial cell cycle progression and tumor cell proliferation.
Enriched Terms Visualization:
Moreover, the MGI Mammalian Phenotype terms such as Chromosomal Instability MP:0008866 (Library: MGI_Mammalian_Phenotype_Level_4_2024 Rank: 1) and Abnormal Mitosis MP:0004046 (Library: MGI_Mammalian_Phenotype_Level_4_2024 Rank: 2) suggest that disruptions in these processes could lead to chromosomal instability, a common feature in cancer biology, further linking the two gene sets through their shared focus on cell cycle dynamics and proliferation.
In summary, the significant overlap between these gene sets is likely due to their mutual emphasis on cell cycle regulation and proliferation, which are critical in both endothelial cell differentiation and tumor response to immunotherapy.
Hypothesis 2: PMC5077964-oncotarget-07-31623-s004.xlsx-Cluster3_DW_Nutlin_Nutlin_Wip1i-Gene_Symbol;GSE159694-3-vs-0-human up
The high overlap between the Rummagene set and the RummaGEO set can be attributed to their shared focus on cell cycle regulation and DNA replication processes, which are critical in both endothelial cell differentiation and cancer cell proliferation.
The RummaGEO gene set, GSE159694-3-vs-0-human up, involves genes that are upregulated in endothelial cells during the late G1 phase compared to untreated endothelial cells derived from human embryonic stem cells (hESCs). This study highlights the role of retinoic acid in promoting an early G1 state, which is crucial for hemogenic endothelial cell specification. The focus on cell cycle phases, particularly the transition from G1 to S phase, is essential for understanding how endothelial cells progress through the cell cycle and differentiate.
On the other hand, the Rummagene set, PMC5077964-oncotarget-07-31623-s004.xlsx-Cluster3_DW_Nutlin_Nutlin_Wip1i-Gene_Symbol, is derived from a study investigating the cooperation of Nutlin-3a and a Wip1 inhibitor to enhance p53 activity. This study emphasizes the importance of p53 in tumor suppression and cell cycle regulation, particularly in the context of inhibiting Mdm2 and Wip1 to enhance p53-mediated responses. The combination of these inhibitors leads to increased expression of p53 target genes, cell senescence, and G2/M phase accumulation, highlighting the role of cell cycle checkpoints in cancer therapy.
The enriched terms from the overlapping genes further support this connection. Terms such as Cell Cycle WP179 (Library: WikiPathway_2023_Human Rank: 2), DNA Replication WP466 (Library: WikiPathway_2023_Human Rank: 3), and DNA Metabolic Process (GO:0006259) (Library: GO_Biological_Process_2023 Rank: 1) indicate a shared involvement in cell cycle regulation and DNA replication. These processes are crucial for both the differentiation of endothelial cells and the proliferation of cancer cells. Additionally, the presence of terms like Retinoblastoma Gene In Cancer WP2446 (Library: WikiPathway_2023_Human Rank: 1) and Mitotic Sister Chromatid Segregation (GO:0000070) (Library: GO_Biological_Process_2023 Rank: 3) suggests a link between cell cycle dysregulation and cancer, which is relevant to both studies.
Enriched Terms Visualization:
In summary, the significant overlap between these gene sets can be explained by their mutual focus on cell cycle regulation and DNA replication, which are pivotal in both endothelial cell differentiation and cancer cell proliferation. The enriched terms highlight the shared biological processes and pathways that underpin these phenomena, providing a mechanistic basis for the observed overlap.
The high overlap between the Rummagene set and the RummaGEO set can be attributed to shared biological processes and cellular mechanisms that are relevant to both endothelial cell cycle regulation and liver hepatocellular carcinoma (LIHC) stem cell characteristics.
The RummaGEO gene set, GSE159694-3-vs-0-human up, focuses on genes upregulated in endothelial cells during the late G1 phase compared to untreated endothelial cells derived from human embryonic stem cells (hESCs). This study highlights the role of retinoic acid in promoting an early G1 state, which is crucial for hemogenic endothelial cell specification. The emphasis on cell cycle phases suggests a focus on cell proliferation and differentiation processes.
On the other hand, the Rummagene set, PMC11025768-pone.0298004.s003.xlsx-Sheet1-Unnamed_0, is derived from a study that integrates single-cell and bulk RNA-seq data to identify stem cell signatures in LIHC. The study aims to construct a prognostic model based on cancer stem cell (CSC)-associated genes, which are linked to tumor recurrence, metastasis, and treatment resistance. The focus here is on stemness, cell cycle regulation, and the impact of these factors on patient prognosis and treatment strategies.
The enriched terms from the overlapping genes provide further insight into the connection between these two gene sets. Terms such as Retinoblastoma Gene In Cancer WP2446 (Library: WikiPathway_2023_Human Rank: 1) and Cell Cycle WP179 (Library: WikiPathway_2023_Human Rank: 2) indicate a shared involvement in cell cycle regulation and cancer-related pathways. The presence of DNA Metabolic Process (GO:0006259) (Library: GO_Biological_Process_2023 Rank: 1) and DNA Repair (GO:0006281) (Library: GO_Biological_Process_2023 Rank: 2) suggests that both gene sets are involved in maintaining genomic stability, which is crucial for both endothelial cell differentiation and cancer stem cell survival. Additionally, terms like Chromosomal Instability MP:0008866 (Library: MGI_Mammalian_Phenotype_Level_4_2024 Rank: 1) and Abnormal Mitosis MP:0004046 (Library: MGI_Mammalian_Phenotype_Level_4_2024 Rank: 2) highlight the potential for dysregulated cell division, a common feature in both cancer progression and stem cell biology.
Enriched Terms Visualization:
In summary, the significant overlap between these gene sets can be attributed to their shared focus on cell cycle regulation, genomic stability, and the biological processes that underpin both endothelial cell differentiation and cancer stem cell characteristics. These commonalities are reflected in the enriched terms, which highlight pathways and processes relevant to both contexts.
The high overlap between the Rummagene set and the RummaGEO set can be attributed to their shared focus on cell cycle regulation and the involvement of specific regulatory complexes and pathways.
The RummaGEO gene set, GSE159694-3-vs-2-human up, involves genes that are upregulated in endothelial cells during the late G1 phase compared to the G2 phase, derived from human embryonic stem cells (hESCs). This study highlights the role of retinoic acid in promoting an early G1 state, which is crucial for the specification of hemogenic endothelial cells. The focus on cell cycle phases, particularly the transition from G1 to G2, is central to understanding how endothelial cells progress through the cell cycle and how this progression can be modulated to influence cell fate decisions.
The Rummagene set, PMC10634886-media-5.xlsx-LIN37_Uxa_et_al_2019-genename, examines the repression of cell-cycle genes by the DREAM and E2F:RB complexes, independent of HDAC activity. The study investigates the role of these complexes in regulating G1/S and G2/M cell-cycle genes, particularly in the context of cell-cycle arrest. The gene set includes differentially expressed genes in SIN3B−/−, SIN3A knockdown, and SIN3B−/−;SIN3A knockdown HCT116 cells, highlighting the impact of these genetic modifications on cell-cycle gene expression.
The enriched terms from the overlapping genes further support the connection between these two gene sets. The presence of terms such as Cell Cycle WP179 (Library: WikiPathway_2023_Human Rank: 3) and Positive Regulation Of Cell Cycle Process (GO:0090068) (Library: GO_Biological_Process_2023 Rank: 2) indicates a shared involvement in cell cycle regulation. Additionally, the term Retinoblastoma Gene In Cancer WP2446 (Library: WikiPathway_2023_Human Rank: 1) suggests a link to the E2F:RB complex, which is a key player in the Rummagene study. The enrichment of Mitotic Sister Chromatid Segregation (GO:0000070) (Library: GO_Biological_Process_2023 Rank: 1) and Microtubule Cytoskeleton Organization Involved In Mitosis (GO:1902850) (Library: GO_Biological_Process_2023 Rank: 3) reflects the importance of precise cell cycle control and chromosomal dynamics, which are relevant to both endothelial cell cycle progression and the repression of cell-cycle genes by the DREAM and E2F:RB complexes.
Enriched Terms Visualization:
Overall, the significant overlap between these gene sets can be attributed to their mutual focus on the regulation of cell cycle processes, particularly the transition between different phases, and the involvement of key regulatory complexes and pathways that govern these transitions.