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Runx3 restoration regresses K-Ras–activated mouse lung cancers and inhibits recurrence

ABSTRACT: Comparision of the gene expression profiles of the RUNX3 Knock out and RUNX3 restored cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE243968 | GEO | 2023/11/02

REPOSITORIES: GEO

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Runx3 Restoration Regresses K-Ras-Activated Mouse Lung Cancers and Inhibits Recurrence.

Project description:Oncogenic K-RAS mutations occur in approximately 25% of human lung cancers and are most frequently found in codon 12 (G12C, G12V, and G12D). Mutated K-RAS inhibitors have shown beneficial results in many patients; however, the inhibitors specifically target K-RASG12C and acquired resistance is a common occurrence. Therefore, new treatments targeting all kinds of oncogenic K-RAS mutations with a durable response are needed. RUNX3 acts as a pioneer factor of the restriction (R)-point, which is critical for the life and death of cells. RUNX3 is inactivated in most K-RAS-activated mouse and human lung cancers. Deletion of mouse lung Runx3 induces adenomas (ADs) and facilitates the development of K-Ras-activated adenocarcinomas (ADCs). In this study, conditional restoration of Runx3 in an established K-Ras-activated mouse lung cancer model regressed both ADs and ADCs and suppressed cancer recurrence, markedly increasing mouse survival. Runx3 restoration suppressed K-Ras-activated lung cancer mainly through Arf-p53 pathway-mediated apoptosis and partly through p53-independent inhibition of proliferation. This study provides in vivo evidence supporting RUNX3 as a therapeutic tool for the treatment of K-RAS-activated lung cancers with a durable response.

| S-EPMC10605764 | biostudies-literature

Runx3 restoration regresses K-Ras–activated mouse lung cancers and inhibits recurrence

Project description:Runx3 restoration regresses K-Ras–activated mouse lung cancers and inhibits recurrence

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Next Generation Sequencing (RNA-Sequencing) for the analysis of RUNX3 and YAP1 targets in TGFb-stimulated HEK 293 cells

Project description:Comparision of the gene expression profiles of the TGFb-stimulated and si-Con, si-RUNX3 and si-YAP1 treated cells.

2023-11-09 | GSE226590 | GEO

Increased expression of RUNX3 inhibits normal human myeloid development

Project description:In this study, RUNX3 expression was analyzed in normal and malignant haematopoiesis and the impact of its dysregulation on myelopoiesis was further determined. We found that RUNX3 was highly expressed in haematopoietic progenitors, with its levels reducing towards granulocytic differentiation. In AML, RUNX3 was overexpressed across all different subtypes except in core binding factor AML where it was downregulated. RUNX3 overexpression in human haematopoietic stem and progenitor cells (HSPC) inhibited myeloid development, particularly granulopoiesis. Further RNA-sequencing studies showed that RUNX3 overexpression downregulates key hematopoietic genes, while upregulating certain lymphoid genes. Overall, this study suggests that increased RUNX3 expression could contribute to the myeloid block characteristic of AML by possibly driving a competing transcriptional program favoring the lymphoid fate.

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Runx3 function in IL-2-activated splenic CD8+ T cells

Project description:CD8+T cells are immune cells that recognize foreign antigens on infected and tumor cells, leading to cytokine-dependent expansion and activation of cytotoxicity towards the targets. To identify Runx3 regulated genes, CD8+ T cells were isolated from spleen of WT and Runx3-/- mice . Six samples (3 WT and 3 Runx3-/-) of CD8+ T cells were separately obtained from individual mice, TCR activated and cultured for 4 days with IL-2.

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Runx3 function in splenic NK cells activated in vivo by IL-15.

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2014-01-22 | E-GEOD-50120 | biostudies-arrayexpress

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Project description:ChIP-seq was conducted using splenic WT NK cells cultured for 7 days with IL-2 using anti-Runx3 antibodies (Ab), anti-H3K4me1 Ab and non-immune serum (NIS) as control. Two biological Runx3, one H3K4me1 and two NIS IP repeats from splenic NK cells isolated from individual mice by negative selection using NK cell isolation kit (R&D) cultured with IL-2.

2013-11-18 | E-GEOD-50129 | biostudies-arrayexpress

Genome-wide maps of Runx3 bound regions in splenic IL-2-activated CD8+ T cells

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2013-11-18 | E-GEOD-50128 | biostudies-arrayexpress

The interactomes of RUNX1 and RUNX3 from Mus musculus T cells

Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.

2019-11-12 | PXD007511 | Pride

Genome-wide maps of Runx3 bound regions in splenic NK cells activated in vivo with IL-15

Project description:ChIP-seq was conducted using freshly isolated splenic WT NK cells from IL-15/Ra treated mice with anti-Runx3 antibody (Ab) and non-immune serum (NIS) as control. Runx3 and NIS IP from splenic NK cells of IL-15/Ra treated WT mice, isolated by negative selection using NK cell isolation kit (R&D) followed by sorting of NKp46+ cells.

2014-01-22 | E-GEOD-50126 | biostudies-arrayexpress

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