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Impact of genetic depletion or pharmacological inhibition of LSD1 on gene expression in ovarian cancer cells [CUT&Tag]

ABSTRACT: LSD1 is frequently overexpressed and correlates with poor prognosis in patients with ovarian cancer. RNA-seq, CUT&Tag-seq and ATAC-seq were performed to determine the impact of genetic depletion or pharmacological inhibition of LSD1 on gene expresion profiles in ovarian cancer cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE218796 | GEO | 2023/10/20

REPOSITORIES: GEO

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Impact of genetic depletion or pharmacological inhibition of LSD1 on gene expression in ovarian cancer cells [ATAC-Seq]

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Chromatin profiling upon pharmacological LSD1 inhibition in MCC [CUT&RUN]

Project description:Merkel cell carcinoma (MCC) is a highly aggressive, neuroendocrine skin cancer that lacks actionable mutations, which could be utilized for targeted therapies. Epigenetic regulators governing cell identity may represent unexplored therapeutic entry points. Here, we targeted epigenetic regulators in a pharmacological screen and discovered that the lysine-specific histone demethylase 1A (LSD1/KDM1A) is required for MCC growth in vitro and in vivo. We show that LSD1 inhibition in MCC disrupts the LSD1-CoREST complex leading to displacement and degradation of HMG20B (BRAF35), a poorly characterized complex member that is essential for MCC proliferation. Inhibition of LSD1 causes derepression of transcriptional master regulators of the neuronal lineage, activates a gene expression signature resembling normal Merkel cells, and induces cell cycle arrest and cell death. Our study unveils the importance of LSD1 for proliferation and maintaining cell identity in MCC. There is growing evidence that cancer cells exploit cellular plasticity and dedifferentiation programs to evade destruction by the immune system. The combination of LSD1 inhibitors with checkpoint inhibitors may thus represent a promising treatment strategy for MCC patients.

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Project description:The experiment contains CUT&Tag profiles for transcription factor HNF4A in HT29 cell line treated with shRNA for PINK1. The experiment also include a control profile for HNF4A in HepG2 cell line.

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Bulk Cut&run and Cut&tag

Project description:Bulk Cut&run and Cut&tag

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