Conclusion
Overall, LSD1 functions as a cancer stem cell supporter in OSCC by catalyzing demethylation of miR-17 and activating the downstream KPNA2/PI3K/AKT pathway, which contributes to understanding of the mechanisms associated with epigenetic regulation in OSCC.
Methods
RT-qPCR detection was firstly conducted to screen out research gene by determining differential expression of histone demethylases and methylases in identified OSCSCs. Then, microarray analysis was carried out in cells with poor expression of LSD1.
Objective
The effects of epigenetic modifiers have been uncovered on cellular reprogramming and, specifically, on sustaining characteristics of cancer stem cells. We here aim to investigate whether lysine-specific demethylase 1 (LSD1) affects the development of oral squamous cell carcinoma (OSCC) by sustaining the cancer stem cells from OSCC (OSCSCs).
Results
OSCSCs expressed high levels of LSD1, and LSD1 inhibition reduced cell viability, migration, invasion, and sphere formation of OSCSCs. Later mechanistic studies suggested that LSD1 inhibited microRNA (miR)-17 expression through histone demethylation. miR-17 bound to KPNA2, and LSD1 downstream genes were mainly enriched in the PI3K/AKT pathway. Importantly, miR-17 inhibitor reversed the inhibitory effect of si-LSD1 on cell activity, while si-KPNA2 abolished the promotive effect of miR-17 inhibitor on cell activity both in vitro and in vivo.