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Tanshinone I inhibit normal and malignant hematopoiesis by repressing EZH2 activity

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Danio rerio Homo sapiens

PROVIDER: GSE155574 | GEO | 2020/08/04

REPOSITORIES: GEO

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Tanshinone I inhibit normal and malignant hematopoiesis by repressing EZH2 activity [zebrafish]

Project description:Purpose: To explore the mechanism of how Tan I inhibits malignant hematopoiesis at the gene expression level Methods: 72 hpf Tg(c-mybhyper: GFP) zebrafish embryos treated with DMSO or Tan I 60 μM were collected for RNA sequencing Results: We found that 1882 genes were differentially expressed between DMSO and Tan I treatment in c-mybhyper fish embryos (p value <=0.05, |log2 fold change| >= 0.25) Conclusions: We identified MMP9 and ABCG2 as two possible downstream genes of Tan I’s effects on EZH2

2020-08-04 | GSE155573 | GEO

Tanshinone I inhibit normal and malignant hematopoiesis by repressing EZH2 activity [human]

Project description:Purpose: To explore the mechanism of how Tan I inhibits malignant hematopoiesis at the gene expression level Methods: NB4 cells treated with DMSO or Tan I 10 μM were collected for RNA sequencing Results: We found that 376 genes were differentially expressed between DMSO and Tan I treatment in the NB4 cells (p value <=0.05, |log2 fold change| >= 0.25) Conclusions: We identified MMP9 and ABCG2 as two possible downstream genes of Tan I’s effects on EZH2

2020-08-04 | GSE155572 | GEO

Tanshinone I inhibit normal and malignant hematopoiesis by repressing EZH2 activity

Project description:Tanshinone I inhibit normal and malignant hematopoiesis by repressing EZH2 activity

| PRJNA650319 | ENA

Tanshinone I inhibit normal and malignant hematopoiesis by repressing EZH2 activity [human]

Project description:Tanshinone I inhibit normal and malignant hematopoiesis by repressing EZH2 activity [human]

| PRJNA650378 | ENA

Tanshinone I inhibit normal and malignant hematopoiesis by repressing EZH2 activity [zebrafish]

Project description:Tanshinone I inhibit normal and malignant hematopoiesis by repressing EZH2 activity [zebrafish]

| PRJNA650379 | ENA

Tanshinone I, a new EZH2 inhibitor restricts normal and malignant hematopoiesis through upregulation of <i>MMP9</i> and <i>ABCG2</i>.

Project description:Rationale: Tanshinone, a type of diterpenes derived from salvia miltiorrhiza, is a particularly promising herbal medicine compound for the treatment of cancers including acute myeloid leukemia (AML). However, the therapeutic function and the underlying mechanism of Tanshinone in AML are not clear, and the toxic effect of Tanshinone limits its clinical application. Methods: Our work utilizes human leukemia cell lines, zebrafish transgenics and xenograft models to study the cellular and molecular mechanisms of how Tanshinone affects normal and abnormal hematopoiesis. WISH, Sudan Black and O-Dianisidine Staining were used to determine the expression of hematopoietic genes on zebrafish embryos. RNA-seq analysis showed that differential expression genes and enrichment gene signature with Tan I treatment. The surface plasmon resonance (SPR) method was used with a BIAcore T200 (GE Healthcare) to measure the binding affinities of Tan I. In vitro methyltransferase assay was performed to verify Tan I inhibits the histone enzymatic activity of the PRC2 complex. ChIP-qPCR assay was used to determine the H3K27me3 level of EZH2 target genes. Results: We found that Tanshinone I (Tan I), one of the Tanshinones, can inhibit the proliferation of human leukemia cells in vitro and in the xenograft zebrafish model, as well as the normal and malignant definitive hematopoiesis in zebrafish. Mechanistic studies illustrate that Tan I regulates normal and malignant hematopoiesis through direct binding to EZH2, a well-known histone H3K27 methyltransferase, and inhibiting PRC2 enzymatic activity. Furthermore, we identified MMP9 and ABCG2 as two possible downstream genes of Tan I's effects on EZH2. Conclusions: Together, this study confirmed that Tan I is a novel EZH2 inhibitor and suggested MMP9 and ABCG2 as two potential therapeutic targets for myeloid malignant diseases.

| S-EPMC8171091 | biostudies-literature

EZH2 in normal hematopoiesis and hematological malignancies.

Project description:Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2, inhibits gene expression through methylation on lysine 27 of histone H3. EZH2 regulates normal hematopoietic stem cell self-renewal and differentiation. EZH2 also controls normal B cell differentiation. EZH2 deregulation has been described in many cancer types including hematological malignancies. Specific small molecules have been recently developed to exploit the oncogenic addiction of tumor cells to EZH2. Their therapeutic potential is currently under evaluation. This review summarizes the roles of EZH2 in normal and pathologic hematological processes and recent advances in the development of EZH2 inhibitors for the personalized treatment of patients with hematological malignancies.

| S-EPMC4823035 | biostudies-literature

Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-09-21 | E-GEOD-73218 | biostudies-arrayexpress

In Vivo Mapping of Notch Pathway Activity in Normal and Stress Hematopoiesis

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-07-01 | E-GEOD-46726 | biostudies-arrayexpress

Epitranscriptomics in Normal and Malignant Hematopoiesis.

Project description:Epitranscriptomics analyze the biochemical modifications borne by RNA and their downstream influence. From this point of view, epitranscriptomics represent a new layer for the control of genetic information and can affect a variety of molecular processes including the cell cycle and the differentiation. In physiological conditions, hematopoiesis is a tightly regulated process that produces differentiated blood cells starting from hematopoietic stem cells. Alteration of this process can occur at different levels in the pathway that leads from the genetic information to the phenotypic manifestation producing malignant hematopoiesis. This review focuses on the role of epitranscriptomic events that are known to be implicated in normal and malignant hematopoiesis, opening a new pathophysiological and therapeutic scenario. Moreover, an evolutionary vision of this mechanism will be provided.

| S-EPMC7555315 | biostudies-literature

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