Similar Datasets
Project description:Expression data of KDM4C knockout by CRISPR in Prostate cancer cell line C4-2B
| PRJNA740242 | ENA
Project description:Histone lysine demethylase KDM4B is often overexpressed in prostate cancer and links to poor survival outcome. Recent evidence suggests that KDM4B serves as a potential therapeutic target. The global transcriptomic analysis between control and KDM4B-knockdown C4-2B cells reveals the metabolic genes involved in Warburg effect are downregulated after knocking down the expression of KDM4B, indicating its role in tumor growth.
2023-03-24 | GSE147481 | GEO
Project description:Gastric cancer (GC) stem cells (GCSCs) are characterized as high level of ALDH activity, however, the mechanisms of maintenance of high ALDH activity and stemness in GCSCs are largely unknown. Here, we report that KDM4C, a H3K9me2/3-demethylase, epigenetically regulates ALDH1A3 by histone demethylation and forms a feed-forward loop with ALDH1A3 to supports GS stemness. Ectopic expression of both KDM4C and ALDH1A3 promotes the properties of GCSCs, including spherogenecity, self-renewal, CD44 expression and ALDH activity; knockdown of anyone abolished the effect of each other. KDM4C directly binds to the promoter of ALDH1A3, leads to histone demethylation, thereby promoting ALDH1A3 transcription. Upregulated ALDH1A3 in turn transcriptionally upregulates KDM4C. Simultaneous inhibition of KDM4C and ALDH1A3 synergistically sensitizes GC sphere-derived cells to traditional chemotherapeutic drugs. The finding that upregulated ALDH1A3 promotes its own transcription via KDM4C-mediated epigenetic modification represents an important feed-forward mechanism for GCSCs to maintain stemness and promote tumourigenesis and our work thus suggests a novel therapeutic strategy for eradicating human GCSCs. To investigate the mechanisms underlying KDM4C promoting CG stemness, we identified the differentially expressed proteins (DEPs) between KDM4C-overexpressing and control AGS cells by iTRAQ-based quantitative proteomic analysis.
2022-02-16 | PXD023455 | Pride
Project description:Epigenetic and genetic regulations are sometimes considered as separate mechanisms that influence gene expression and phenotypes. However, there are DNA sequence variants in epigenetic regulators that could affect gene regulation. The histone demethylase, KDM4C, promotes transcriptional activation by removing the repressive histone mark, tri-methylation of lysine 9 of histone H3 (H3K9me3), from its target genes. In this study, we uncovered cis-acting DNA sequence variants in KDM4C that contribute to individual differences in its expression. Utilizing this natural variation, we performed genetic analyses in B-cells in order to identify target genes that are regulated by KDM4C. We used microarrays to investigate gene expression changes in the target genes from our genetic analyses following knockdown of KDM4C in primary fibroblasts. Primary fibroblasts with stable expression of shRNA targeting KDM4C or a control construct were selected for RNA extraction and hybridization to Affymetrix microarrays. Following selection for stable expression of the shRNA constructs we selected clones expressing 3 non-overlapping constructs targeting KDM4C (shKDM4C) and 2 clones expressing the control construct (shCtr) for analysis by microarray.
2013-09-14 | E-GEOD-41040 | biostudies-arrayexpress
Project description:We have mapped binding sites for the histone demethylase, Jmjd2c/Kdm4c/Gasc1, in mouse embryonic stem cells (ESCs).
2014-01-09 | GSE53936 | GEO
Project description:KDM4C, a histone lysine demethylase, has been proposed to participate in malignant transformation and progression in several types of cancer. However, its roles in hepatocellular carcinoma (HCC) remain poorly understood. In this study, we report that KDM4C protein level is upregulated and KDM4C silencing inhibits cell growth, proliferation and migration in HCC. Furthermore, we provide evidence that depletion of KDM4C leads to defective G2/M checkpoint, increases radiation-induced DNA damage and impairs DNA repair, and enhances radiosensitivity in HCC cells. Using RNA sequencing, we uncover that chemokine CXCL2 is a downstream effector of KDM4C. KDM4C knockdown upregulates the expression of CXCL2 and promotes the secretion of CXCL2 in HCC cells. Importantly, the observed effects caused by KDM4C depletion in HCC cells can be partially rescued by CXCL2 silencing. Thus, our findings demonstrate that KDM4C is involved in the cell migration and radiosensitivity via modulating CXCL2, indicating that KDM4C may be a potential therapeutic target in HCC.
2023-05-03 | GSE189941 | GEO
Project description:Epigenetic and genetic regulations are sometimes considered as separate mechanisms that influence gene expression and phenotypes. However, there are DNA sequence variants in epigenetic regulators that could affect gene regulation. The histone demethylase, KDM4C, promotes transcriptional activation by removing the repressive histone mark, tri-methylation of lysine 9 of histone H3 (H3K9me3), from its target genes. In this study, we uncovered cis-acting DNA sequence variants in KDM4C that contribute to individual differences in its expression. Utilizing this natural variation, we performed genetic analyses in B-cells in order to identify target genes that are regulated by KDM4C. We used microarrays to investigate gene expression changes in the target genes from our genetic analyses following knockdown of KDM4C in primary fibroblasts.
2013-09-14 | GSE41040 | GEO
Project description:Radioresistance is regarded as the main barrier to effective radiotherapy in lung cancer. However, the underlying mechanisms of radioresistance remain elusive. Here, we show that lysine-specific demethylase 4C (KDM4C) is overexpressed and correlated with poor prognosis in lung cancer patients. We provide evidence that genetical or pharmacological inhibition of KDM4C impairs tumorigenesis and radioresistance in lung cancer in vitro and in vivo. Moreover, we uncover that KDM4C upregulates TGFβ2 expression by directly reducing H3K9me3 level at the TGFβ2 promoter and then activates TGF-β/Smad/ATM signaling to confer radioresistance in lung cancer. Using tandem affinity purification technology, we further identify deubiquitinase USP9X as a critical binding partner which deubiquitinates and stabilizes KDM4C. More importantly, depletion of USP9X impairs TGF-β/Smad signaling and radioresistance by destabilizing KDM4C in lung cancer cells. Thus, our findings demonstrate that USP9X-mediated KDM4C deubiquitination activates TGF-β/Smad signaling to promote radioresistance, suggesting that targeting KDM4C may be a promising radiosensitization strategy in the treatment of lung cancer.
2021-07-14 | GSE136404 | GEO
Project description:Transcriptional deregulation plays a major role in acute myeloid leukemia, identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence showing the functional involvement and therapeutic potentials of targeting PRMT1 with H4R3 methyltransferase activity in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C with H3K9 demethylase activity by chimeric transcription factors to mediate epigenetic reprogramming. Inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a novel and targetable epigenetic circuitry mediated by PRMT1 and KDM4C in acute leukemia.
2016-01-14 | E-MTAB-3322 | biostudies-arrayexpress
Project description:We have mapped binding sites for the histone demethylase, Jmjd2c/Kdm4c/Gasc1, in mouse embryonic fibroblasts (MEFs) and the impact of Jmjd2c depletion on H3K9me3 and H3K36me3 distributions.
2014-01-09 | GSE53939 | GEO