Human periodontal ligament cells (hPDLCs) play a vital role in cell regeneration and tissue repair with multi-directional differentiation potential. microRNAs (miRs) are implicated in the osteogenesis of hPDLCs. This study explored the mechanism of miR-143-3p in osteogenesis of hPDLCs. Osteogenic differentiation of isolated hPDLCs was induced. KLF5 expression during osteogenic differentiation of hPDLCs was detected and then silenced in hPDLCs. Binding relationship between KLF5 and miR-143-3p was predicted and verified. hPDLCs were treated with miR-143-3p mimic or overexpressing KLF5, and then osteogenic specific markers and mineralized nodules were measured. The key factors of the Wnt/β-catenin pathway during osteogenesis of hPDLCs were measured. KLF5 expression was upregulated during osteogenesis of hPDLCs. KLF5 silencing or miR-143-3p mimic reduced osteogenic specific markers and mineralized nodules. Overexpression of KLF5 could reverse the inhibitory effect of miR-143-3p on osteogenic differentiation. miR-143-3p mimic and KLF5 silencing inactivated the Wnt/β-catenin pathway. Activation of the Wnt/β-catenin pathway reversed the repression effect of miR-143-3p mimic on osteogenesis of hPDLCs. In conclusion, miR-143-3p inhibited osteogenic differentiation of hPDLCs by targeting KLF5 and inactivating the Wnt/β-catenin pathway.

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.

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