ABSTRACT
Objective:To investigate the effects of bromodomain and extraterminal domain (BET) inhibitor JQ1 combined with siPD-L1 on the proliferation and apoptosis of oral squamous cell carcinoma (OSCC) Scc-25 cells and its mechanism.Methods:Scc-25 cells were cultured in vitro and treated with different concentrations of JQ1 (0, 0.2, 1, 5 μmol/L). Cell proliferation was detected by cell count kit-8 (CCK-8) assay; the expression levels of programmed cell death ligand 1(PD-L1) and forkhead box M1(FoxM1) protein were detected by Western blot. Appropriate concentration of JQ1 was selected for subsequent experiments. Scc-25 cells were divided into four groups: control group (without any treatment), siPD-L1 group (transfected with siPD-L1), JQ1 group (added JQ1 after transfected with non-specific siRNA), and combined treatment group (added JQ1 after transfected with siPD-L1). CCK-8 assay was used to detect the proliferation ability of Scc-25 cells in each group. Western blot was used to detect the expression levels of cleaved caspase-3, PD-L1 and FoxM1, and flow cytometry was used to detect the apoptosis rate of cells in each group. Results:With the increase of JQ1 concentration, the proliferation ability of SCC-25 cells and the expression levels of PD-L1 and FoxM1 decreased gradually (all P<0.01). JQ1 concentration of 1 μmol/L had obvious inhibitory effect on cell proliferation and the expression levels of PD-L1 and FoxM1, so JQ1 concentration of 1 μmol/L was selected for subsequent experiments. The proliferation ability of Scc-25 cells, the expression of PD-L1 and FoxM1 proteins in JQ1 group, siPD-L1 group and combination treatment group were significantly lower than those in the control group (all P<0.01), and the expression of cleaved caspase-3 protein and the rate of apoptosis were significantly higher than those in the control group (all P<0.01); Moreover, the effect of the combination treatment group was more significant than that of siPD-L1 group, JQ1 group (all P<0.01). Conclusions:The combination of JQ1 and siPD-L1 could effectively inhibit the proliferation and promotes the apoptosis of OSCC Scc-25 cells, and its mechanism may be related to the suppression of PD-L1 and FoxM1 signaling pathways.
ABSTRACT
In recent years, the category of atopic dermatitis (AD) has been updated in domestic and foreign guidelines, and elderly AD has been added as a subtype. The pathogenesis of elderly AD is related to heredity, skin barrier dysfunction, immune dysregulation and lifestyle. Most elderly AD patients have atypical clinical symptoms, and misdiagnosis is very common. To fully understand the pathogenesis and clinical characteristics of elderly AD, and to formulate individualized diagnosis and treatment plans based on clinical characteristics, are particularly important for improving the quality of life of patients and reducing the burden of the disease.
ABSTRACT
MicroRNAs (miRNAs) are a class of non-coding RNA molecules that regulate gene expression after transcription and participate in various pathophysiological processes in the skin. In recent years, it has been reported that changes in miRNA expression profiles are related to some inflammatory skin diseases. For example, miR-203, miR-146a and miR-21 are upregulated in psoriatic lesions, miR-155 and miR-146a are upregulated in atopic dermatitis lesions, miR-21, miR-223, miR-142-3p and miR142-5p are upregulated in allergic contact dermatitis lesions; however, miR-146a and miR-155 are downregulated in peripheral blood of patients with systemic lupus erythematosus, and miR-223 is downregulated in dermatomyositis lesions. This review summarizes relationships of miRNAs with the occurrence and development of some inflammatory skin diseases.