EZH2-H3K27me3 mediated KRT14 upregulation promotes TNBC peritoneal metastasis

Verma, Ayushi; Singh, Atul Kumar; Singh, Manish Pratap; Nengroo, Mushtaq Ahmad; Saini, Komal; Satrusal, Saumya Ranjan; Khan, Mohammad Afsar; Chaturvedi, Priyank; Sinha, Abhipsa; Meena, Sanjeev; Singh, Anup K.; Datta, Dipak

doi:10.1038/s41467-022-35059-x

Cited by 54 publications

(30 citation statements)

References 73 publications

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“…KRT14 is positively correlated with the metastasis of triple-negative breast cancer (TNBC), and deletion of KRT14 signi cantly reduces the migration, invasion, and peritoneal metastasis of TNBC [34]. KRT14 is absent in the distal airways of healthy lungs and plays an important role in the human pulmonary epithelial cells of IPF [35,36].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Necroptosis and Immune Infiltration in the Progression of Idiopathic Pulmonary Fibrosis

Fan

Luo

2023

Preprint

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Objective To ascertain the function of necroptosis in IPF (idiopathic pulmonary fibrosis) using bioinformatic techniques. Methods GSE10667 and GSE24206 datasets were obtained from the Gene Expression Omnibus (GEO) database. Necroptosis-related differentially expressed genes (NRDEGs) were identified based on the differentially expressed gene (DEG) and necroptosis gene collection. The gene enrichment signaling pathways in IPF were assessed using gene set enrichment analysis (GSEA). Protein-protein interaction (PPI) networks were created and visualized using the STRING database and Cytoscape, which also identified essential NRDEG functional components. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were used for pathway enrichment analyses of NRDEGs. The necroptosis-related transcription factor-target gene regulatory network was built using the CellMiner database, and immune infiltration patterns were examined using the CIBERSORTx algorithm. Results: IPF samples showed significant enrichment and activation of the necroptosis pathway. PEL1, MEFV, and SERTAD1 were among the 44 NRDEGs identified.Hub genes were abundant in the IL-17 signaling pathway, RIG-I-like receptor signaling pathway, and apoptosis, and the NRDEGs were largely involved in endopeptidase activity and ficolin-1-rich granules. Twenty-two possible immune cells, including neutrophils, NK cells, CD4, and CD8, were elevated in both datasets. Conclusion We found differential genes related to IPF necroptosis and various immune cell infiltrates, among which CHL1, EGFR, and KRT14, and NRDEG-related drugs and compounds might provide new targets for treatment of IPF.

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Section: Discussionmentioning

confidence: 99%

Identification of Novel Necroptosis and Immune Infiltration in the Progression of Idiopathic Pulmonary Fibrosis

Fan

Luo

2023

Preprint

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“…Epigenetic changes are gaining immense prominence as pivotal events in breast cancer progression and metastasis 28 . Our recent findings have revealed the role of epigenetic modulator EZH2 in reshaping the metastatic landscape of TNBC 29 . Additionally, there has been a growing comprehension regarding the crosstalk between metabolic reprogramming and epigenetic mechanisms during the course of cancer progression, epithelial to mesenchymal transition (EMT), and its subsequent metastasis 30, 31 .…”

Section: Introductionmentioning

confidence: 88%

“…All stained slides were examined under EVOS XL core microscope under 10X and 40X magnification. The staining intensity of each section was scored as described previously 29 where 0 (no staining), 1+ (weak staining), 2+ (moderate staining), or 3+ (strong staining). The tumor cell positive rate (0–100%) per slice was multiplied by the staining intensity to get an overall H-scores ranging from 0 to 300.…”

Section: Methodsmentioning

confidence: 99%

ACSL4 activity drives TNBC metastasis by positively regulating Histone H3 Acetylation mediated SNAIL expression

Sinha,

Saini,

Tripathi

et al. 2023

Preprint

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Triple-Negative Breast Cancer (TNBC) has profound unmet medical need globally for its devastating clinical outcome associated with rapid metastasis and lack of targeted therapies. Recently, lipid metabolic reprogramming has emerged as a major driver of breast cancer metastasis. Here, we unveil a strong association between the heightened expression of fatty acid metabolic enzyme, acyl-CoA synthetase 4 (ACSL4) and TNBC, which is primarily attributed by the selective absence of progesterone receptor (PR). Loss of ACSL4 function, either through genetic ablation or pharmacological inhibition significantly reduces metastatic potential of TNBC. Global transcriptome analysis reveals that ACSL4 activity markedly influences the gene expression pattern associated with TNBC migration. Mechanistically, ACSL4 alters fatty acid oxidation (FAO) and cellular acetyl-CoA levels, leading to the hyper- acetylation of particularly H3K27Ac and H3K9Ac marks resulting in overexpression of SNAIL during the course of TNBC metastatic spread to lymph node and lungs. Further, human TNBC metastasis exhibits positive correlation between ACSL4 and SNAIL expression. Altogether, our findings provide new molecular insights regarding the intricate interplay between metabolic alterations and epigenetic modifications, intertwined to orchestrate TNBC metastasis and posit a rational understanding for the development of ACSL4 inhibitors as a targeted therapy against TNBC.

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“…More surprisingly, recent study in mammalian showed that H3K27me3 was also involved in the promotion of gene expression. The deposition of H3K27me3 attenuates binding of repressor SP1 to the promoter of the target gene thus facilitating transcription [36]. EZH2, a H3K27me3 methylase, was revealed to be a transcription activator to activate gene expression but independent of its methyltransferase activity [37].…”

Section: The Unique Feature Of H3k27me3 Enrichment and Function In So...mentioning

confidence: 99%

Dynamics of the epigenetic landscape during development and in response to drought stress in sorghum

Shen

et al. 2023

Preprint

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Sorghum bicolor is a C4 plant with the characteristics of high stress tolerance. In this study, we investigated the differential enrichment of 7 histone marks in leaf and root as well as in response to PEG treatment in the two organs, and revealed some epigenomic features that have never been reported before. For example, the long H3K27me3 regions clustered in four areas, which we defined as H3K27me3 islands, were identified in sorghum. The increase of some H3K27me3 enrichment was associated with gene up-regulation in leaf but not in root. H3K36me3 plays some role in inhibiting the deposition of both H3K27me3 and H2A.Z, which may serve as partial motivation for the removal of H3K27me3 and H2A.Z in leaf and root, but was not involved in the prevention of H3K27me3 spreading into a long region. Finally, we analyzed histone mark variation in the genes that were differentially expressed both between leaf and root and in response to PEG treatment (defined as common DEGs), and found that most of the changes of histone marks occurred in some common DEGs in leaf and root could not be observed in the same genes in response to PEG treatment.

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EZH2-H3K27me3 mediated KRT14 upregulation promotes TNBC peritoneal metastasis

Cited by 54 publications

References 73 publications

Identification of Novel Necroptosis and Immune Infiltration in the Progression of Idiopathic Pulmonary Fibrosis

Identification of Novel Necroptosis and Immune Infiltration in the Progression of Idiopathic Pulmonary Fibrosis

ACSL4 activity drives TNBC metastasis by positively regulating Histone H3 Acetylation mediated SNAIL expression

Dynamics of the epigenetic landscape during development and in response to drought stress in sorghum

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