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Targeting KDM4A epigenetically activates tumor cell-intrinsic immunity and overcomes resistance to PD1 blockade in squamous cell carcinoma by inducing DNA replication stress

ABSTRACT: Targeting KDM4A epigenetically activates tumor cell-intrinsic immunity and overcomes resistance to PD1 blockade in squamous cell carcinoma by inducing DNA replication stress

PROVIDER: PRJNA573945 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10180839.fastq.gz	Fastqsanger.gz
	SRR10180840.fastq.gz	Fastqsanger.gz
	SRR10180841.fastq.gz	Fastqsanger.gz
	SRR10180842.fastq.gz	Fastqsanger.gz

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Targeting KDM4A epigenetically activates tumor cell-intrinsic immunity and overcomes resistance to PD1 blockade in squamous cell carcinoma by inducing DNA replication stress

Project description:To investigate the mechanisms by which KDM4A knockout ameliorates the invasive growth and metastasis of primary mouse squamous cell carcinoma (SCC), we isolated fresh SCCs from tumor cell-specific KDM4A knockout and control mice, and then did the whole transcriptome analysis using RNA-Seq. Results showed that KDM4A knockout stimulated anti-tumor immunity.

2021-03-23 | GSE137953 | GEO

Efficient Elimination of Acute Myeloid Leukaemia Cells through Inhibition of KDM4A

Project description:We previously identified an essential role for the H3K9me3 histone demethylase, KDM4A, in maintaining AML cell survival, with genetic depletion by shRNA of KDM4A inducing leukaemic cell death with little effect on normal haematopoiesis. We hypothesised KDM4A inhibition may represent a novel and effective strategy to treat AML. To address this, we provided proof-of-principle for the use of KDM4 inhibitors (KDM4Ai) and fully characterised their functional potential in AML cells and identified the epigenetic mechanisms underpinning the essential role of KDM4A activity in THP-1 cells using both ChIP-seq and RNA-seq, delineating and functionally validating the epigenomic network regulated by KDM4A, showing that selective loss of KDM4A is sufficient to induce apoptosis in a broad spectrum of human AML cells. This detrimental phenotype results from a global accumulation of H3K9me3 and H3K27me3 at KDM4A targeted genomic loci thereby causing down-regulation of a KDM4A-PAF1 controlled transcriptional program essential for leukemogenesis, distinct from that of KDM4C.

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MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells

Project description:MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells

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miRNA expression between CD4+PD1+ and CD4+PD1- T cells

Project description:Recent success in cancer immunotherapy has come from the blockade of inhibitory receptors on T cells, such as programmed cell death-1, which can induce a state of T cell exhaustion upon constant antigen stimulation. Understanding miRNA regulation of PD1 can be useful to discover miRNAs for use in therapy or as prognostic markers in various diseases including cancer, autoimmunity and transplantation. We used microarrays to discover global miRNA expression changes upon PD1 upregulation and identified miRNAs that are both up- and down-regulated. B16F10 cells were injected subcutaneously into C57BL/6 mice and 16 days later CD4+PD1+ and CD4+PD1- were sorted from the lymph nodes and spleen for RNA extraction and hybridization on Affymetrix miRNA array.

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Project description:To establish a robust cellular model system for screening genes associated with cell invasion, we over-expressed the oncogenic translocated promoter region (Tpr)-MET proteins in SCC23 cells (SCC23/MET). Using a functional siRNA screen, we identified that the histone demethylase KDM4A played a critical role in the invasive growth and metastasis of SCC mediated by the Oncogenic MET. To investigate the molecular mechanism through which KDM4A inhibit the tumor cell invasion, we knock-down KDM4A in SCC23/MET cell and performed a gene microarray to examine which genes may be regulaged by kDM4A. We generated two stable cell lines. one was infected with virus containing scramble and another infected with virus infected with virus containing KDM4A shRNA. Total RNA were extracted from these two cell lines and subject to microarray.

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MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [France3]

Project description:MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [France3]

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MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [France4]

Project description:MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [France4]

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KDM4A regulated gene expression in human prostate cancer LNCaP cell

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