Similar Datasets
Project description:We previously identified that MLL3, also known as lysine methyltransferase 2C, is frequently mutated in Upper Aerodigestive Squamous Cell Carcinoma (UASCC). TCGA dataset also demonstrated that around 10% of UASCC patients have a mutation of MLL3. However, the significance of MLL3 in the context of premalignant biology and neoplastic evolution has not been well understood. Therefore, we aim to explore the functional contribution of MLL3 to the biology of UASCC in this study. We identified that MLL3 forms a protein complex with GRHL2 in the regulation of UASCC epigenome. To investigate the regulation of the downstream signaling pathway by MLL3/GRHL2 protein complex, ChIP sequencing using either MLL3 or GRHL2 antibodies was performed in UASCC cell line. In addition, either MLL3 or GRHL2 was silenced by transfection of siRNA and performed RNA-Sequencing in UASCC cell line (KYSE510) to profile the transcriptome.
2024-07-20 | GSE238118 | GEO
Project description:We previously identified that MLL3, also known as lysine methyltransferase 2C, is frequently mutated in Upper Aerodigestive Squamous Cell Carcinoma (UASCC). TCGA dataset also demonstrated that around 10% of UASCC patients have a mutation of MLL3. However, the significance of MLL3 in the context of premalignant biology and neoplastic evolution has not been well understood. Therefore, we aim to explore the functional contribution of MLL3 to the biology of UASCC in this study. We identified that MLL3 forms a protein complex with GRHL2 in the regulation of UASCC epigenome. To investigate the regulation of the downstream signaling pathway by MLL3/GRHL2 protein complex, ChIP sequencing using either MLL3 or GRHL2 antibodies was performed in UASCC cell line. In addition, either MLL3 or GRHL2 was silenced by transfection of siRNA and performed RNA-Sequencing in UASCC cell line (KYSE510) to profile the transcriptome.
2024-07-20 | GSE238111 | GEO
Project description:The MLL3/GRHL2 complex regulates early malignant transformation and anti-tumor immunity in squamous cancer
| PRJNA997986 | ENA
Project description:The MLL3/GRHL2 complex regulates early malignant transformation and anti-tumor immunity in squamous cancer [ChIP-seq]
| PRJNA997987 | ENA
Project description:The MLL3/GRHL2 complex regulates early malignant transformation and anti-tumor immunity in squamous cancer [RNA-seq]
| PRJNA997988 | ENA
Project description:Cancer associated with smoking and drinking remains a serious health problem worldwide. The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC).FOXM1 mRNA and protein expressions were investigated in four independent cohorts (total 75 patients) consisting of normal, premalignant and HNSCC tissues and cells using quantitative PCR (qPCR), expression microarray, immunohistochemistry and immunocytochemistry. Effect of putative oral carcinogens on FOXM1 transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblotting and short-hairpin RNA interference. Genome-wide single nucleotide polymorphism (SNP) array was used to 'trace' the genomic instability signature pattern in 8 clonal lines of FOXM1-induced malignant human oral keratinocytes. Furthermore, acute FOXM1 upregulation in primary oral keratinocytes directly induced genomic instability. We have shown for the first time that overexpression of FOXM1 precedes HNSCC malignancy. Screening putative carcinogens in human oral keratinocytes surprisingly showed that nicotine, which is not perceived to be a human carcinogen, directly induced FOXM1 mRNA, protein stabilisation and transcriptional activity at concentrations relevant to tobacco chewers. Importantly, nicotine also augmented FOXM1-induced transformation of human oral keratinocytes. A centrosomal protein CEP55 and a DNA helicase/putative stem cell marker HELLS, both located within a consensus loci (10q23), were found to be novel targets of FOXM1 and their expression correlated tightly with HNSCC progression.This study cautions the potential co-carcinogenic effect of nicotine in tobacco replacement therapies. We hypothesise that aberrant upregulation of FOXM1 may be inducing genomic instability through a program of malignant transformation involving the activation of CEP55 and HELLS which may facilitate aberrant mitosis and epigenetic modifications. Our finding that FOXM1 is upregulated early during oral cancer progression renders FOXM1 an attractive diagnostic biomarker for early cancer detection and its candidate mechanistic targets, CEP55 and HELLS, as indicators of malignant conversion and progression.
| S-EPMC2654098 | biostudies-literature
Project description:Genome-wide SNP profilling for loss of heterozygosity (LOH) during FOXM1B-induced malignant transformation in a human premalignant oral keratinocyte line SVpgC2a. Keywords: oral cancer, keratinocytes, head and neck squamous cell carcinoma, FOXM1, genomic instability, SNP array, loss of heterozygosity, malignant transformation
2009-06-13 | GSE11782 | GEO
Project description:"Oncometabolite" 2-hydroxyglutarate (2-HG) is an aberrant metabolite found in tumor cells, exerting a pivotal influence on tumor progression. Recent studies have unveiled its impact on the proliferation, activation, and differentiation of anti-tumor T cells. Moreover, 2-HG regulates the function of innate immune components, including macrophages, dendritic cells, natural killer cells, and the complement system. Elevated levels of 2-HG hinder α-KG-dependent dioxygenases (α-KGDDs), contributing to tumorigenesis by disrupting epigenetic regulation, genome integrity, hypoxia-inducible factors (HIF) signaling, and cellular metabolism. The chiral molecular structure of 2-HG produces two enantiomers: D-2-HG and L-2-HG, each with distinct origins and biological functions. Efforts to inhibit D-2-HG and leverage the potential of L-2-HG have demonstrated efficacy in cancer immunotherapy. This review delves into the metabolism, biological functions, and impacts on the tumor immune microenvironment (TIME) of 2-HG, providing a comprehensive exploration of the intricate relationship between 2-HG and antitumor immunity. Additionally, we examine the potential clinical applications of targeted therapy for 2-HG, highlighting recent breakthroughs as well as the existing challenges.
| S-EPMC10826830 | biostudies-literature
Project description:Tumors escape immune surveillance by inducing various immunosuppressive pathways, including the activation of inhibitory receptors on tumor-infiltrating T cells. While monoclonal antibodies (mAbs) blocking programmed cell death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have been approved for multiple cancer indications, only a subset of patients benefit from immune checkpoint blockade therapies, highlighting the need for additional approaches. Therefore, the identification of new target molecules acting in distinct or complementary pathways in monotherapy or combination therapy with PD-1/PD-L1 blockade is gaining immense interest. T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT) has received considerable attention in cancer immunotherapy. Recently, anti-TIGIT mAb (tiragolumab) has demonstrated promising clinical efficacy in non-small cell lung cancer treatment when combined with an anti-PD-L1 drug (Tecentriq), leading to phase III trial initiation. TIGIT is expressed mainly on T and natural killer cells; it functions as an inhibitory checkpoint receptor, thereby limiting adaptive and innate immunity. CD226 competes for binding with the same ligands with TIGIT but delivers a positive stimulatory signal to the immune cells. This review discusses the recent discoveries regarding the roles of TIGIT and CD226 in immune cell function and their potential application in cancer immunotherapy.
| S-EPMC7997242 | biostudies-literature
Project description:PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells. VE-cadherin, an endothelial marker of vascular normalization, was up-regulated in HUVEC treated with PARP inhibitors or following PARP-1 silencing; vimentin over-expression was sufficient to drive to an EndoMT phenotype. In melanoma cells, PARP inhibition reduced pro-metastatic markers, including vasculogenic mimicry. We also demonstrated that vimentin expression was sufficient to induce increased mesenchymal/pro-metastasic phenotypic changes in melanoma cells, including ILK/GSK3-β-dependent E-cadherin down-regulation, Snail1 activation and increased cell motility and migration. In a murine model of metastatic melanoma, PARP inhibition counteracted the ability of melanoma cells to metastasize to the lung. These results suggest that inhibition of PARP interferes with key metastasis-promoting processes, leading to suppression of invasion and colonization of distal organs by aggressive metastatic cells.
| S-EPMC3681683 | biostudies-literature