microRNA‐17 is a tumor suppressor in oral squamous cell carcinoma and is repressed by LSD1

Abstract

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). 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. 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. 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.

Silencing KPNA2 Promotes Ferroptosis in Laryngeal Cancer by Activating the FoxO Signaling Pathway

“…However, ferroptosis has been less studied in laryngeal cancer, and more research is needed to prove the effect of ferroptosis in laryngeal cancer. Karyopherin α2 (KPNA2) expression is elevated in a variety of tumors, such as non-small cell lung cancer [12], breast cancer[13], hepatocellular carcinoma [14], oral squamous cell carcinoma [15], etc., promoting the proliferation, migration, invasion and epithelial-mesenchymal transformation of tumor cells. Therefore, KPNA2 can be regarded as a tumor biomarker and therapeutic target [16][17][18].…”