Analysis of miRNAs in MCF7 cells regulated by LSD1
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE218200 | GEO | 2024/03/04
REPOSITORIES: GEO
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Project description:Lysine specific demethylase 1 (LSD1) is an important histone demethylase that mediates metastasis in luminal breast cancer. Exosomes play a major role in cell-to-cell communication. Thus, the characterization of miRNAs of exosome in MCF7 cells regulated by LSD1 is imperative in clarifying intercellular signaling.
2024-03-04 | GSE212291 | GEO
Project description:Lysine-specific demethylase 1 (LSD1) is a histone demethylase that promotes stemness and cancer cell survival, including in prostate cancer. Most prostate malignancies are adenocarcinomas with luminal differentiation. However, a subset of tumors undergoes cellular reprogramming to a more lethal neuroendocrine prostate cancer (NEPC) with neuronal differentiation. The frequency of NEPC is increasing since widespread use of potent androgen receptor signaling inhibitors. Currently, there are no effective treatments for NEPC. We previously determined that LSD1 promotes survival of prostate adenocarcinoma tumors. However, role of LSD1 in NEPC is largely unknown. We sought to identify key genes and molecular pathways controlled by LSD1 in NEPC. We therefore inhibited LSD1 with SP2509 and performed RNA-seq in LASCPC-01, LNCaP-N-Myc, and MR42D cell lines. The vast majority of differentially expressed genes after SP2509 treatment were upregulated, suggesting that LSD1 may primarily function as a transcriptional repressor in NEPC. RNA-seq analysis reveals that LSD1 represses pathways linked to luminal differentiation and TP53 is the top pathway reactivated after LSD1 suppression. Taken together, these data suggest that LSD1 may be an important regulator of TP53 function in prostate cancer.
2023-08-30 | GSE218993 | GEO
Project description:LSD1 (KDM1A) is a histone demethylase that plays both oncogenic and tumor suppressor roles in breast cancer. However, the exact contexts under which it plays these opposite roles remain largely elusive. By characterizing its role in normal and cancerous luminal mammary epithelial cells (MECs), here we show that LSD1 is essential for maintaining differentiation and survival of luminal cells. LSD1-inhibition by both genetic and pharmacological approaches increases invasion of luminal breast cancer cells. Mechanistically, we find LSD1 interacts with GATA3 and their common target genes are highly related to breast cancer. LSD1 positively regulates GATA3 expression and represses that of TRIM37, a histone H2A ubiquitin ligase and breast cancer oncoprotein. LSD1-loss leads to reduced expression of several cell junction genes (e.g., CDH1, VCL, CTNNA1), possibly via TRIM37-mediated repression. Collectively, our data suggest LSD1 largely plays a tumor suppressor role in luminal breast cancer and the increased MEC invasiveness associated with LSD1-inhibition can be blocked via TRIM37-inhibition.
2019-08-16 | GSE95165 | GEO
Project description:Although there are plenty of researches about nucleic acid in small extracellular vesicles (sEVs), properties of proteins identified as sEVs’ cargos and the mechanism of their action in recipient cell are poorly understood. Here, we show that lysine specific demethylase 1 (LSD1), the first identified histone demethylase in 2004, existed in the cell cultured medium of gastric cancer cells. Further investigation confirmed the presence of LSD1 in sEVs from gastric cancer cells and gastric cancer patient plasma, which is the first identified histone demethylase in sEVs. By shuttling from donor cells to recipient gastric cancer cells, sEVs-delivered LSD1 promoted the cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2 and CD44, and suppressed the oxaliplatin response of the recipient cells in vitro and in vivo, while LSD1 depleted sEVs failed to suppress the oxaliplatin response. Collectively, our findings give an evidence for LSD1 as a sEVs protein to promote stemness and suppress oxaliplatin response for the first time and constitute a future avenue to predict oxaliplatin response in gastric cancer clinically.
2021-12-22 | PXD020223 | Pride
Project description:Although there are plenty of researches about nucleic acid in small extracellular vesicles (sEVs), properties of proteins identified as sEVs’ cargos and the mechanism of their action in recipient cell are poorly understood. Here, we show that lysine specific demethylase 1 (LSD1), the first identified histone demethylase in 2004, existed in the cell cultured medium of gastric cancer cells. Further investigation confirmed the presence of LSD1 in sEVs from gastric cancer cells and gastric cancer patient plasma, which is the first identified histone demethylase in sEVs. By shuttling from donor cells to recipient gastric cancer cells, sEVs-delivered LSD1 promoted the cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2 and CD44, and suppressed the oxaliplatin response of the recipient cells in vitro and in vivo, while LSD1 depleted sEVs failed to suppress the oxaliplatin response. Collectively, our findings give an evidence for LSD1 as a sEVs protein to promote stemness and suppress oxaliplatin response for the first time and constitute a future avenue to predict oxaliplatin response in gastric cancer clinically.
2021-07-30 | PXD021511 | Pride
Project description:The role of histone lysine methylation in estrogen receptor-alpha (ERα)-activated transcription is highly context-specific and poorly understood. Here, we show that lysine demethylase 1 (LSD1) mediates loss of H3 lysine 4 dimethylation (H3K4me2) in coordination with tripartite-motif-containing protein 24 (TRIM24)- regulated growth of breaset cancer-derived cells. We performed global profiling of histone H3K4me2 in comparison to genome-wide binding of TRIM24 in MCF7 cells when estrogen is depleted or added. We found specific subsets of genes with functions in transcription and cell proliferation are depleted of H3K4me2 at TRIM24 binding sites. Chromatin immunoprecipitation (ChIP) analyses over a time course of estrogen induction revealed cyclic demethylation of H3K4me2, LSD1, TRIM24 and ERα binding. Inhibition of LSD1 enzymatic activity led to increased H3K4me2 and decreased estrogen response of TRIM24-dependent genes. Additon of a small molecule inhibitor of the TRIM24 bromodomain or depletion of TRIM24 expression amplified the impact of LSD1 inhbition as measured by survival and proliferation of MCF7 cells, suggesting that combinatorial inhibition of LSD1 and TRIM24 may be effective in targeting ER-positive breast cancers.
2019-12-01 | GSE113654 | GEO
Project description:Heterochromatin is a specialized form of chromatin that restricts access to DNA and inhibits genetic processes, including transcription and recombination. In Neurospora crassa, constitutive heterochromatin is characterized by trimethylation of lysine 9 on histone H3, hypoacetylation of histones, and DNA methylation. Here we explore whether the conserved histone demethylase, lysine-specific demethylase 1 (LSD1), regulates heterochromatin in Neurospora, and if so, how. Though LSD1 is implicated in heterochromatin regulation, its function is inconsistent across different systems; orthologs of LSD1 have been shown to either promote or antagonize heterochromatin expansion by removing H3K4me or H3K9me respectively. We identify three members of the Neurospora LSD complex (LSDC): LSD1, PHF1, and BDP-1, and strains deficient for any exhibit variable spreading of heterochromatin and establishment of new heterochromatin domains dispersed across the genome. Heterochromatin establishment outside of canonical domains in Neurospora share the unusual characteristic of DNA methylation-dependent H3K9me3; typically, H3K9me3 establishment is independent of DNA methylation. Consistent with this, the hyper-H3K9me3 phenotype of LSD1 knock-out strains is dependent on the presence of DNA methylation, as well as HCHC-mediated histone deacetylation, suggesting spreading is dependent on some feedback mechanism. Altogether, our results suggest LSD1 works in opposition to HCHC to maintain proper heterochromatin boundaries.
2021-07-21 | PXD017300 | Pride
Project description:Tumor-initiating cells (TICs) play a critical role in glioblastoma (GBM) maintenance being responsible for its heterogeneity and resistance to standard therapy. A step toward clinical translation includes GBM TIC targeting. Among the molecules tested for GBM treatment, are those targeting epigenetic modifiers. By using patient-derived TICs and xenograft orthotopic models, we identified Lysine-specific histone demethylase 1A (LSD1) as a potentially druggable target in GBM. LSD1-directed therapy by means of the selective, orally bioavailable and brain penetrant inhibitor DDP_38003 effectively impairs growth, stem-like features and tumorigenic potential of GBM TICs. Our findings point to LSD1 as a positive regulator of Activating Transcription Factor 4 (ATF4)-dependent response in all stress conditions arising during tumor growth and therapy. Thus, through the downregulation of either ATF4 and its adaptive genes, LSD1 targeting is likely a promising strategy to hit GBM TICs by counteracting the ATF4-mediated adaptation to stress.
2022-06-02 | PXD021429 | Pride
Project description:Lysine-specific demethylase 1 (LSD1) is a histone demethylase that promotes stemness and cancer cell survival, including in prostate cancer. LSD1 has been shown to perfrom catalytic independent function sto promote prostate cancer survival. Here, we tested the levels of LSD1's canonical target H3K4me2 upon LSD1 inhibition with SP2509 across the genome using CUT and RUN analysis.
2023-08-30 | GSE235211 | GEO
Project description:These proteomic data were produced in order to assess the effect of drug 3324, a pan-lysine demethylase inhibitor, on the estrogen receptor (ER) and Lysine Demethylase1 (LSD1)protein interaction networks.
2021-09-08 | PXD012781 | Pride