Gene expression data in total mRNA from human SKMEL28 melanoma cell line transduced with shCont, shp16, shATR
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE291421 | GEO | 2025/03/12
REPOSITORIES: GEO
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Project description:p16/CDKN2A is a critical cell cycle regulator and tumor suppressor that is lost in ~50% of all human cancers. Recent studies have identified roles of p16 outside of the cell cycle. Understanding the fundamental biology of p16 loss in cancer may provide novel targets to exploit for therapy.
2023-09-24 | GSE243717 | GEO
Project description:Transformed and tumorigenic cells require increased deoxyribonucleotide synthesis to fuel the genome replication that sustains their unregulated cell cycle and proliferation. Therefore, it is likely that the cell cycle and nucleotide metabolism are linked. The cell cycle inhibitor p16 is a critical tumor suppressor that is lost as an early event in many human cancers. While loss of p16 is known to play a role in deregulating the cell cycle, whether loss of p16 expression affects nucleotide metabolism is unknown.
2019-07-02 | GSE133660 | GEO
Project description:*Objectives:* In addition to their well-known role in the control of cellular proliferation and cancer, cell cycle regulators are increasingly identified as important metabolic modulators. Genome wide association studies identified SNPs near the cell cycle regulator CDKN2A/p16INK4a (p16) as strongly associated with risk of developing type 2 diabetes (T2D). T2D is associated with numerous perturbations of hepatic lipid and glucose metabolism. We have recently shown that p16 controls fasting-induced hepatic gluconeogenesis in mice. However, whether p16 may also affect hepatic lipid homeostasis is unknown. *Results:* In primary hepatocytes, p16-deficiency was associated with elevated expression of genes involved in fatty acid catabolism and enhanced activation of PPAR. This led to increased mitochondrial fatty acid oxidation (FAO) through a mechanism requiring the catalytic AMPK 2 subunit and SIRT1. By contrast, *p16* overexpression was associated with triglyceride accumulation and increased lipid droplet numbers *in vitro*, and decreased ketogenesis and hepatic mitochondrial activity *in vivo*. Gene expression analysis of human liver samples revealed a negative correlation between *CDKN2A* expression and *PPARA* and its target genes, suggesting a potential association between hepatic p16 expression and FAO in obese humans. *Conclusions:* Our findings demonstrate that p16 plays a key role in hepatic lipid metabolism and may thus contribute to the development of metabolic diseases.
2020-10-09 | GSE134625 | GEO
Project description:PTPRD is a tumor suppressor of glioma that is frequently co-deleted with CDKN2A/p16. We show that Ptprd and p16 cooperate to promote gliomagenesis in the RCAS PDGFB / Nestin tv-A glioma mouse model. We found unique gene expression changes within tumor cells of Ptprd+/-p16-/- vs. Ptprd+/+p16-/- and Ptprd-/-p16-/- tumor cells.
2014-06-02 | GSE55061 | GEO
Project description:The cyclin-dependent kinase inhibitor p16INK4a (CDKN2A) is an important tumor-suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal. 27 samples were analyzed to study three histone modifications (H3K4me3, H3K9me3, H3K27me3) in three different cell lines. Each combination of histone modification and cell line had three biological replicates (A,B,C).
2010-05-19 | E-GEOD-14436 | biostudies-arrayexpress
Project description:The cyclin-dependent kinase inhibitor p16INK4a (CDKN2A) is an important tumor-suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal.
2009-12-01 | GSE14436 | GEO
Project description:PTPRD is a tumor suppressor of glioma that is frequently co-deleted with CDKN2A/p16. We show that Ptprd and p16 cooperate to promote gliomagenesis in the RCAS PDGFB / Nestin tv-A glioma mouse model. We found unique gene expression changes within tumor cells of Ptprd+/-p16-/- vs. Ptprd+/+p16-/- and Ptprd-/-p16-/- tumor cells. Neonatal mice were injected with RCAS PDGFB GFP. At symptoms, or at 12 weeks post injection, GFP+DAPI- tumor cells were sorted for RNA extraction and hybridization on Affymetrix microarrays. The mouse strain used was a mixed background of C57/BL6 and FVB/N. Ptprd mice were from Uetani et al. 2000 and p16/Nestin-tvA mice were from Tchouganouva et al. 2007.
2014-06-02 | E-GEOD-55061 | biostudies-arrayexpress
Project description:Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation in the absence of genetic mutations is not clear. To investigate this question, we use a CRISPR/dCas9 based epigenetic editing tool, where an inactive form of Cas9 is fused to DNMT3A and its regulator DNMT3L. Using this system, we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary myoepithelial cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct and results in sustained repression of CDKN2A and RASSF1 transcripts which prevents cells from entering senescence. The phenotype is associated with retuned expression of a subset of genes to levels in early passage cells; however, the outgrowing myoepithelial cells are not immortal but proliferate for 25-30 population doublings before cell cycle arrest. Finally, we show that the key driver of this phenotype is repression of CDKN2A transcript p16, but prolonged proliferation is enhanced by combined hypermethylation and repression of both CDKN2A transcripts p16 and p14. This work demonstrates that hit-and-run epigenetic events can prevent senescence entry, a potential first step in the disease process.
2017-08-07 | GSE100208 | GEO
Project description:Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation in the absence of genetic mutations is not clear. To investigate this question, we use a CRISPR/dCas9 based epigenetic editing tool, where an inactive form of Cas9 is fused to DNMT3A and its regulator DNMT3L. Using this system, we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary myoepithelial cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct and results in sustained repression of CDKN2A and RASSF1 transcripts which prevents cells from entering senescence. The phenotype is associated with retuned expression of a subset of genes to levels in early passage cells; however, the outgrowing myoepithelial cells are not immortal but proliferate for 25-30 population doublings before cell cycle arrest. Finally, we show that the key driver of this phenotype is repression of CDKN2A transcript p16, but prolonged proliferation is enhanced by combined hypermethylation and repression of both CDKN2A transcripts p16 and p14. This work demonstrates that hit-and-run epigenetic events can prevent senescence entry, a potential first step in the disease process.
2017-08-07 | GSE100184 | GEO
Project description:Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation in the absence of genetic mutations is not clear. To investigate this question, we use a CRISPR/dCas9 based epigenetic editing tool, where an inactive form of Cas9 is fused to DNMT3A and its regulator DNMT3L. Using this system, we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary myoepithelial cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct and results in sustained repression of CDKN2A and RASSF1 transcripts which prevents cells from entering senescence. The phenotype is associated with retuned expression of a subset of genes to levels in early passage cells; however, the outgrowing myoepithelial cells are not immortal but proliferate for 18-20 population doublings before cell cycle arrest. Finally, we show that the key driver of this phenotype is repression of CDKN2A transcript p16, but prolonged proliferation is enhanced by combined hypermethylation and repression of both CDKN2A transcripts p16 and p14. This work demonstrates that hit-and-run epigenetic events can prevent senescence entry, a potential first step in the disease process.
2017-08-07 | GSE100027 | GEO