Background: Circular RNAs (circRNAs), a group of covalently closed non-coding RNAs, serve critical regulatory roles in many human cancers, including oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate the functional role of circular RNA ITCH (circ-ITCH) in OSCC and the underlying mechanisms. Methods: RT-qPCR analysis was applied to detect the expression levels of circ-ITCH in OSCC tissues and cell lines. MTT assay and flow cytometer analysis were used to evaluate the effects of circ-ITCH overexpression on the proliferation and apoptosis of OSCC cells. Bioinformatics analysis and dual-luciferase reporter assay were applied to determine the binding relation between circ-ITCH and miR-421 as well as PDCD4 mRNA and miR-421. Results: Our results showed that circ-ITCH expression was remarkably decreased in OSCC tissues and cell lines. Low circ-ITCH expression was strongly associated with adverse clinicopathological characteristics of OSCC patients. Moreover, functional assays demonstrated that circ-ITCH overexpression significantly inhibited OSCC cell proliferation and induced cell apoptosis. Our data further uncovered that circ-ITCH could bind directly to miR-421 and block its repression on PDCD4 in OSCC. MiR-421 expression was significantly increased in OSCC tissues and was inversely correlated with circ-ITCH expression. Notably, miR-421 restoration blocked the tumor-suppressive role of circ-ITCH in OSCC cells. Conclusion: In conclusion, our study reveals that circ-ITCH serves as a tumor suppressor in OSCC partly by regulating miR-421/PDCD4 axis.
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.
LncRNA MAFG‐AS1 is predicted to interact with miR‐146a, which can target Toll‐like receptor 4 (TLR4), a key player in periodontitis. This study aimed to investigate the roles of MAFG‐AS1 in periodontitis. It was observed that MAFG‐AS1 was downregulated in the human periodontal ligament stem cells (PDLSCs) derived from periodontitis‐affected teeth. Dual‐luciferase assay revealed that co‐transfection of MAFG‐AS1 expression vector and miR‐146a mimic showed significantly lower relative luciferase activity comparing to co‐transfection of MAFG‐AS1 expression vector and negative control (NC) miRNA. However, MAFG‐AS1 and miR‐146a failed to affect each other. Interestingly, MAFG‐AS1 overexpression led to the upregulated TLR4. In addition, MAFG‐AS1 overexpression also led to the inhibited proliferation of PDLSCs. Therefore, MAFG‐AS1 may regulate the proliferation of PDLSCs and the expression of TLR4 to participate in periodontitis.
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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