Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA145919 | ENA |
REPOSITORIES: ENA
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Project description:To investigate the specific roles of HDAC2 in the development of gastric cancer, we employed large-scale gene expression analysis to identify the molecular signature that may affect enabling characteristics of cancer cells. Differentially expressed genes were analyzed on the MKN-1 cells transfected with HDAC2 shRNAs, and recapitulated molecular signatures that related to hallmarks of cancer. DNA methylation of p16INK4a promoter region was assessed by methylation specific polymerase chain reaction. Recruiting the HDAC2 at the p16INK4a promoter was identified using chromatin immunoprecipitation assay. RNA interference-mediated protein knockdown method was used to investigate oncogenic potential of HDAC2 in in vitro and in vivo gastrocarcinogenesis of MKN-1 cells. RNA interference-mediated protein knockdown versus mock treatment
2011-08-16 | E-GEOD-31338 | biostudies-arrayexpress
Project description:To investigate the specific roles of HDAC2 in the development of gastric cancer, we employed large-scale gene expression analysis to identify the molecular signature that may affect enabling characteristics of cancer cells. Differentially expressed genes were analyzed on the MKN-1 cells transfected with HDAC2 shRNAs, and recapitulated molecular signatures that related to hallmarks of cancer. DNA methylation of p16INK4a promoter region was assessed by methylation specific polymerase chain reaction. Recruiting the HDAC2 at the p16INK4a promoter was identified using chromatin immunoprecipitation assay. RNA interference-mediated protein knockdown method was used to investigate oncogenic potential of HDAC2 in in vitro and in vivo gastrocarcinogenesis of MKN-1 cells.
2011-08-17 | GSE31338 | GEO
Project description:Histone lactylation, an epigenetic modification, promotes tumor growth and immune evasion in various cancers. Our study found increased pan-lysine lactylation and H3K18la in gastric tissues, linked to poor prognosis. Inhibiting glycolysis and silencing lactate dehydrogenase reduced H3K18la, boosting CD8+ T-cell activity against gastric cancer. H3K18la activated HAS2 transcription, enhancing MYC nuclear transport and PD-L1 expression..Our data provide a molecular framework for Histone lactylation in the process of gastric cancer.
2025-09-30 | GSE295142 | GEO
Project description:Knockdown of BHLHE40 expression significantly reduced primary tumor growth and spontaneous lung metastasis in an orthotopic xenograft model of human breast cancer. Gene expression analysis implicated a role of BHLHE40 in hypoxia-induced exosomic secretion of Heparin Binding Epidermal Growth Factor HBEGF, which promotes cell survival and invasion. BHLHE40 induces HBEGF transcription by blocking DNA binding of HDAC1 and HDAC2.
2018-10-30 | GSE107300 | GEO
Project description:Cellular senescence plays a causal role in ageing and, in mouse, depletion of p16INK4a-expressing senescent cells delays ageing-associated disorders. Adenosine deaminases acting on RNA (ADARs) RNA editing enzymes are also implicated as important regulators of human ageing and ADAR inactivation causes age-associated pathologies such as neurodegeneration in model organisms. However, the role, if any, of ADARs in cellular senescence is unknown. Here we show that ADAR1 is post-transcriptionally downregulated by autophagic degradation to promote senescence through upregulating p16INK4a. ADAR1 is downregulated during senescence post-transcriptionally by autophagy-lysosomal pathway and the downregulation is sufficient to drive senescence in both in vitro and in vivo models. Senescence induced by ADAR1 downregulation is p16INK4a dependent and independent of its RNA editing function. Mechanistically, ADAR1 promotes SIRT1 expression by affecting its RNA stability through HuR, an RNA binding protein that increases the half-life and steady state levels of its target mRNAs. And SIRT1, in turn, antagonizes translation of mRNA encoding p16INK4a. Hence, downregulation of ADAR1 and SIRT1 mediates p16INK4aupregulation by enhancing its mRNA translation. Finally, Adar1 is downregulated during ageing of mouse tissues such as brain, ovary, and intestine, and Adar1 expression correlates with Sirt1 expression in these tissues in mice. Together, our study reveals an RNA-editing independent role of ADAR1 in regulating senescence by post-transcriptionally controlling p16INK4a expression.
2022-04-25 | GSE179423 | GEO
Project description:Gastric cancer is one of the most common causes of cancer-related death worldwide. The N6-methyladenosine (m6A) reader IGF2BP1 (insulin-like growth factor-2 mRNA binding protein 1) has been reported to promote cancer progression by stabilizing oncogenic mRNAs through its m6A-binding activity in some tumors. However, the role of IGF2BP1 in gastric carcinogenesis remains unclear. In this study, we find that IGF2BP1 is significantly downregulated in tumor tissues from patients with gastric cancer. Lower expression of IGF2BP1 is associated with poor prognosis. IGF2BP1 suppresses gastric cancer cell proliferation in an m6A-dependent manner. Additionally, IGF2BP1 is able to significantly attenuate tumor growth of gastric cancer cells. Further m6A sequencing and m6A-RIP (RNA immunoprecipitation) assays show that MYC (c-myc proto-oncogene) mRNA is a target transcript of IGF2BP1 in gastric cancer cells. IGF2BP1 inhibits gastric cancer cell proliferation by reducing the mRNA and protein expression of MYC. Mechanistically, IGF2BP1 promotes the degradation of MYC mRNA and inhibits its translation efficiency. Taken together, these data suggest that IGF2BP1 plays a tumor-suppressive role in gastric carcinogenesis by downregulating MYC in an m6A-dependent manner, thereby making the IGF2BP1-MYC axis a potential target for gastric cancer treatment.
2024-02-26 | GSE243617 | GEO
Project description:Non-small cell lung cancer (NSCLC) has a poor prognosis and effective therapeutic strategies are lacking. The diabetes drug canagliflozin inhibits NSCLC cell proliferation and the mammalian target of rapamycin (mTOR) pathway, which mediates cell growth and survival, but it is unclear whether this drug can enhance response rates when combined with cytotoxic therapy. Here, we evaluated the effects of canagliflozin on human NSCLC response to cytotoxic therapy in tissue cultures and xenografts. Ribonucleic acid sequencing (RNA-seq), real-time quantitative PCR (RT-qPCR), metabolic function, small interfering ribonucleic acid (siRNA) knockdown and protein expression assays were used in mechanistic analyses. We found that canagliflozin inhibited proliferation and clonogenic survival of NSCLC cells, and augmented the efficacy of radiotherapy to mediate these effects and inhibit NSCLC xenograft growth. Canagliflozin treatment alone moderately inhibited mitochondrial oxidative phosphorylation and exhibited greater anti-proliferative capacity than specific mitochondrial complex-I inhibitors. The treament downregulated genes mediating hypoxia-inducible factor (HIF)-1a stability, metabolism and survival, activated adenosine monophosphate-activated protein kinase (AMPK) and inhibited mTOR, a critical activator of HIF-1a signaling. HIF-1a knockdown and stabilization experiments suggested that canagliflozin mediates anti-proliferative effects, in part, through suppression of HIF-1a. Transcriptional regulatory network analysis pinpointed histone deacetylase 2 (HDAC2), a gene suppressed by canagliflozin, as a key mediator of canagliflozin’s transcriptional reprogramming. HDAC2 knockdown eliminated HIF-1a levels and enhanced the anti-proliferative effects of canagliflozin. HDAC2-regulated genes suppressed by canagliflozin are associated with poor prognosis in several clinical NSCLC datasets. In addition, we include evidence that canagliflozin also improves NSCLC response to chemotherapy. In summary, canagliflozin may be a promising therapy to develop in combination with cytotoxic therapy in NSCLC.
2023-08-17 | GSE239495 | GEO
Project description:DNA N6-methyladenine (6mA) is an emerging epigenetic modification that regulates various biological processes. Here, we demonstrated the role of DNA 6mA modification in gastric cancer (GC). GC cells and tumors displayed a marked reduction in 6mA levels compared with normal gastric tissues and GES1 cells. 6mA-IP-seq revealed that 6mA was abundant in the surrounding transcription start sites and occurred at consensus motifs. Among the 6mA regulators, ALKBH1, a demethylase, was significantly overexpressed in GC tissues compared to adjacent normal tissues (n=32, P<0.05). Moreover, high ALKBH1 expression was associated with poor survival of patients with GC in three independent GC cohorts (cohort I: n=276, P=0.0093; cohort II: n=136, P=0.001; TCGA dataset: n=381, P=0.0061). Functionally, ALKBH1 knockout increased DNA 6mA and suppressed GC cell growth and cell migration in vitro, and inhibited tumorigenicity and metastasis in vivo. ALKBH1 knockout in mice impairs chemically induced gastric carcinogenesis. Mechanistically, ALKBH1 mediates DNA 6mA demethylation to repress gene expression. In particular, the 6mA sites were enriched in NRF1 binding sequences and targeted for demethylation by ALKBH1. ALKBH1-induced 6mA demethylation inhibited NRF1-driven transcription of downstream targets, including multiple genes involved in the AMPK signaling pathway. Accordingly, ALKBH1 suppressed AMPK signaling, causing a metabolic shift towards the Warburg effect that facilitates tumorigenesis. In conclusion, we revealed, for the first time, that ALKBH1 plays an oncogenic role in GC. ALKBH1 demethylates 6mA within the NRF1-binding regions of tumor suppressor genes to attenuate the binding of NRF1, which subsequently inactivates AMPK signaling and promotes the “Warburg” phenotype.
2025-09-22 | GSE214126 | GEO
Project description:DNA N6-methyladenine (6mA) is an emerging epigenetic modification that regulates various biological processes. Here, we demonstrated the role of DNA 6mA modification in gastric cancer (GC). GC cells and tumors displayed a marked reduction in 6mA levels compared with normal gastric tissues and GES1 cells. 6mA-IP-seq revealed that 6mA was abundant in the surrounding transcription start sites and occurred at consensus motifs. Among the 6mA regulators, ALKBH1, a demethylase, was significantly overexpressed in GC tissues compared to adjacent normal tissues (n=32, P<0.05). Moreover, high ALKBH1 expression was associated with poor survival of patients with GC in three independent GC cohorts (cohort I: n=276, P=0.0093; cohort II: n=136, P=0.001; TCGA dataset: n=381, P=0.0061). Functionally, ALKBH1 knockout increased DNA 6mA and suppressed GC cell growth and cell migration in vitro, and inhibited tumorigenicity and metastasis in vivo. ALKBH1 knockout in mice impairs chemically induced gastric carcinogenesis. Mechanistically, ALKBH1 mediates DNA 6mA demethylation to repress gene expression. In particular, the 6mA sites were enriched in NRF1 binding sequences and targeted for demethylation by ALKBH1. ALKBH1-induced 6mA demethylation inhibited NRF1-driven transcription of downstream targets, including multiple genes involved in the AMPK signaling pathway. Accordingly, ALKBH1 suppressed AMPK signaling, causing a metabolic shift towards the Warburg effect that facilitates tumorigenesis. In conclusion, we revealed, for the first time, that ALKBH1 plays an oncogenic role in GC. ALKBH1 demethylates 6mA within the NRF1-binding regions of tumor suppressor genes to attenuate the binding of NRF1, which subsequently inactivates AMPK signaling and promotes the “Warburg” phenotype.
2025-09-22 | GSE214125 | GEO
Project description:Although gastric cancer is a leading cause of cancer-related deaths, systemic treatment strategies remain scarce. Here, we report the pro-tumorigenic properties of the crosstalk between intestinal tuft cells and type 2 innate lymphoid cells (ILC2) that is evolutionarily optimized for epithelial remodeling in response to helminth infection. We demonstrate that tuft cell-derived interleukin 25 (IL25) drives ILC2 activation, inducing the release of IL13 and promoting tuft cell hyperplasia. This reciprocal tuft cell - ILC2 circuit promotes early gastric metaplasia and tumor formation while genetic ablation of tuft cells, ILC2s or therapeutic targeting of IL13 or IL25 alleviates these phenotypes. Importantly, tuft cell and ILC2 gene signatures predict worsening survival in intestinal-type gastric cancer patients, with ~50% of these tumors showing enrichment for tuft cells and ILC2s. Thus, we reveal an unanticipated function of the tuft cell - ILC2 circuit in promoting multiple steps towards gastric carcinogenesis. Together, this may provide an opportunity to therapeutically inhibit early-stage gastric cancer through repurposing antibody-mediated therapies.
2023-09-25 | GSE217498 | GEO