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Analysis of cellular and exosomal circRNAs in MCF7 cells regulated by LSD1 (RNA-Seq)

ABSTRACT: Lysine-specific demethylase 1 (LSD1), a histone demethylating enzyme, plays a crucial role in cancer metastasis. While studies have demonstrated that the knockout of LSD1 significantly enhances lung metastasis of breast cancer cells, it remains unclear whether LSD1-deficient breast cancer cells can remodel the lung microenvironment to allow metastasis. In this study, we isolated exosomes from LSD1-knockdown breast cancer cells (LSD1 KD) and investigated their effects on the formation of pre-metastatic niches. The intravenous injection of exosomes from LSD1 KD cells in mice resulted in a substantial increase in lung colonization by breast cancer cells, while treatment with exosomes derived from LSD1 KD cells decreased the expression of the tight junction proteins ZO-1 and occludin in vascular endothelial cells, leading to increased pulmonary vascular permeability. In addition, the knockdown of LSD1 reduced the expression of the circular RNA circDOCK1, which augmented the levels of miR-1270 in exosomes. Further investigation showed that miR-1270 inhibited ZO-1 expression in human umbilical vein endothelial cells, which enhanced their permeability. In conclusion, our study uncovered a novel mechanism in which the epigenetic modifier LSD1 promotes the formation of pre-metastatic niches via the regulation of exosomal miRNA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE264699 | GEO | 2024/09/12

REPOSITORIES: GEO

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Analysis of cellular and exosomal miRNAs in MCF7 cells regulated by LSD1 (miRNA-Seq)

Project description:Lysine-specific demethylase 1 (LSD1), a histone demethylating enzyme, plays a crucial role in cancer metastasis. While studies have demonstrated that the knockout of LSD1 significantly enhances lung metastasis of breast cancer cells, it remains unclear whether LSD1-deficient breast cancer cells can remodel the lung microenvironment to allow metastasis. In this study, we isolated exosomes from LSD1-knockdown breast cancer cells (LSD1 KD) and investigated their effects on the formation of pre-metastatic niches. The intravenous injection of exosomes from LSD1 KD cells in mice resulted in a substantial increase in lung colonization by breast cancer cells, while treatment with exosomes derived from LSD1 KD cells decreased the expression of the tight junction proteins ZO-1 and occludin in vascular endothelial cells, leading to increased pulmonary vascular permeability. In addition, the knockdown of LSD1 reduced the expression of the circular RNA circDOCK1, which augmented the levels of miR-1270 in exosomes. Further investigation showed that miR-1270 inhibited ZO-1 expression in human umbilical vein endothelial cells, which enhanced their permeability. In conclusion, our study uncovered a novel mechanism in which the epigenetic modifier LSD1 promotes the formation of pre-metastatic niches via the regulation of exosomal miRNA.

2024-09-12 | GSE264698 | GEO

LSD1 inhibits the invasion and migration of breast cancer through exosomes

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2024-07-31 | GSE266982 | GEO

Analysis of exosomal miRNAs in MCF7 cells regulated by LSD1

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.

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OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis [RNA-seq]

Project description:Genomic amplification of OTUD7B is frequently found across human cancers. But its role in tumorigenesis is poorly understood. Lysine‐specific demethylase 1 (LSD1) is known to execute epigenetic regulation by forming corepressor complex with CoREST/histone deacetylases (HDACs). However, the molecular mechanisms by which cells maintain LSD1/CoREST complex integrity are unknown. Here, it is reported that LSD1 protein undergoes K63‐linked polyubiquitination. OTUD7B is responsible for LSD1 deubiquitination at K226/277 residues, resulting in dynamic control of LSD1 binding partner specificity and cellular homeostasis. OTUD7B deficiency increases K63‐linked ubiquitination of LSD1, which disrupts LSD1/CoREST complex formation and targets LSD1 for p62‐mediated proteolysis. Consequently, OTUD7B deficiency impairs genome‐wide LSD1 occupancy and enhances the methylation of H3K4/H3K9, therefore profoundly impacting global gene expression and abrogating breast cancer metastasis. Moreover, physiological fluctuation of OTUD7B modulates cell cycle‐dependent LSD1 oscillation, ensuring the G1/S transition. Both OTUD7B and LSD1 proteins are overpresented in high‐grade or metastatic human breast cancer, while dysregulation of either protein is associated with poor survival and metastasis. Thus, OTUD7B plays a unique partner‐switching role in maintaining the integrity of LSD1/CoREST corepressor complex, LSD1 turnover, and breast cancer metastasis.

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OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis [ChIP-seq]

2021-04-20 | GSE172369 | GEO

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2024-03-04 | GSE218200 | GEO

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