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

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.