Transcriptional landscape of oncogene-induced senescence: a machine learning-based meta-analytic approach

Han, Yeaeun; Micklem, Gos; Kim, Sung Young

doi:10.1016/j.arr.2023.101849

Cited by 8 publications

(5 citation statements)

References 74 publications

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“…The enriched pathways (i.e., populated by GPR19-upregulated proteins) represented either oncogene-induced cell senescence or nuclear lamina breakdown. Hence, at this point, GPR19 appears to be marshaling activities linked to negative cell fates associated with oncogenesis or pro-aging phenotypes linked to nuclear breakdown that are characteristic of accelerated aging programs [151][152][153][154]. Hence, within the dose-series of GPR19 expression, we found a potent degree of linkage between GPR19 functionality and the aging-based triumvirate of "DDR-oncology-energy metabolism".…”

Section: Discussionmentioning

confidence: 76%

GPR19 Coordinates Multiple Molecular Aspects of Stress Responses Associated with the Aging Process

Maudsley

Schrauwen

Harputluoğlu

et al. 2023

IJMS

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G protein-coupled receptors (GPCRs) play a significant role in controlling biological paradigms such as aging and aging-related disease. We have previously identified receptor signaling systems that are specifically associated with controlling molecular pathologies associated with the aging process. Here, we have identified a pseudo-orphan GPCR, G protein-coupled receptor 19 (GPR19), that is sensitive to many molecular aspects of the aging process. Through an in-depth molecular investigation process that involved proteomic, molecular biological, and advanced informatic experimentation, this study found that the functionality of GPR19 is specifically linked to sensory, protective, and remedial signaling systems associated with aging-related pathology. This study suggests that the activity of this receptor may play a role in mitigating the effects of aging-related pathology by promoting protective and remedial signaling systems. GPR19 expression variation demonstrates variability in the molecular activity in this larger process. At low expression levels in HEK293 cells, GPR19 expression regulates signaling paradigms linked with stress responses and metabolic responses to these. At higher expression levels, GPR19 expression co-regulates systems involved in sensing and repairing DNA damage, while at the highest levels of GPR19 expression, a functional link to processes of cellular senescence is seen. In this manner, GPR19 may function as a coordinator of aging-associated metabolic dysfunction, stress response, DNA integrity management, and eventual senescence.

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Section: Discussionmentioning

confidence: 76%

GPR19 Coordinates Multiple Molecular Aspects of Stress Responses Associated with the Aging Process

Maudsley

Schrauwen

Harputluoğlu

et al. 2023

IJMS

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“…Pro-NPCs: progenitor NPCs, marked with ACAN , SOX9 , UBE2C, and TOP2A ; Fibro- NPCs: fibrotic NPCs, marked with ACAN , SOX9 , FBLN1 34 , 35 ; IR-NPCs: integral regulatory NPCs, marked with ACAN , SOX9 , CH3L2 36 ; Met-NPCs: metabolic NPCs, marked with ACAN , SOX9 , DKK1 37 ; Adh-NPCs: adhesive NPCs, marked with ACAN , SOX9, and MSMO1 36 ; and SR-NPCs: stress-responsive NPCs, marked with ACAN , SOX9, and CP .…”

Section: Resultsmentioning

confidence: 99%

Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration

Chen,

Lei,

Chen

et al. 2024

Nat Commun

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Intervertebral disc degeneration is a natural process during aging and a leading cause of lower back pain. Here, we generate a comprehensive atlas of nucleus pulposus cells using single-cell RNA-seq analysis of human nucleus pulposus tissues (three males and four females, age 41.14 ± 18.01 years). We identify fibrotic late-stage nucleus pulposus cells characterized by upregulation of serglycin expression which facilitate the local inflammatory response by promoting the infiltration of inflammatory cytokines and macrophages. Finally, we discover that daphnetin, a potential serglycin ligand, substantially mitigates the local inflammatory response by downregulating serglycin expression in an in vivo mouse model, thus alleviating intervertebral disc degeneration. Taken together, we identify late-stage nucleus pulposus cells and confirm the potential mechanism by which serglycin regulates intervertebral disc degeneration. Our findings indicate that serglycin is a latent biomarker of intervertebral disc degeneration and may contribute to development of diagnostic and therapeutic strategies.

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“…FBLN family genes code for ECM proteins responsible for maintaining tissue structure as a component of the basement membrane and elastic fibers [ 18 ]. Among them, FBLN1 is closely associated with tumor cell migration, adhesion, and invasion [ 19 , 20 ]. PTGDS belongs to the lipocalin superfamily of lipid carrier proteins and plays dual roles in prostaglandin metabolism and lipid transport [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA combined with Bulk RNA analysis to explore oxidative stress and energy metabolism factors and found a new prostatic cancer oncogene MXRA8

Miao,

Song,

Jin

et al. 2024

Aging

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Background: Prostate cancer is the most common malignancy among men worldwide, and its diagnosis and treatment are challenging due to its heterogeneity.Methods: Integrating single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data, we identified two molecular subtypes of prostate cancer based on dysregulated genes involved in oxidative stress and energy metabolism. We constructed a risk score model (OMR) using common differentially expressed genes, which effectively evaluated prostate cancer prognosis. Results: Our analysis demonstrated a significant correlation between the risk score model and various factors, including tumor immune microenvironment, genomic variations, chemotherapy resistance, and immune response. Notably, patients with low-risk scores exhibited increased sensitivity to chemotherapy and immunotherapy compared to those with high-risk scores, indicating the model’s potential to predict patient response to treatment. Additionally, our investigation of MXRA8 in prostate cancer showed significant upregulation of this gene in the disease as confirmed by PCR and immunohistochemistry. Functional assays including CCK-8, transwell, plate cloning, and ROS generation assay demonstrated that depletion of MXRA8 reduced the proliferative, invasive, migratory capabilities of PC-3 cells, as well as their ROS generation capacity. Conclusions: Our study highlights the potential of oxidative stress and energy metabolism-related genes as prognostic markers and therapeutic targets in prostate cancer. The integration of scRNA-seq and bulk RNA-seq data enables a better understanding of prostate cancer heterogeneity and promotes personalized treatment development. Additionally, we identified a novel oncogene MXRA8 in prostate cancer.

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Transcriptional landscape of oncogene-induced senescence: a machine learning-based meta-analytic approach

Cited by 8 publications

References 74 publications

GPR19 Coordinates Multiple Molecular Aspects of Stress Responses Associated with the Aging Process

GPR19 Coordinates Multiple Molecular Aspects of Stress Responses Associated with the Aging Process

Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration

Single-cell RNA combined with Bulk RNA analysis to explore oxidative stress and energy metabolism factors and found a new prostatic cancer oncogene MXRA8

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