LncRNA DLEU1 facilitates the progression of oral squamous cell carcinoma by miR-126-5p/GAB1 axis.

Oral squamous cell carcinoma (OSCC) is one of the most frequent malignancies found in head and neck cancers. Dysregulation of lncRNAs has been proposed to be related to the development of OSCC. Here, we investigated the function and probable mechanisms of lncRNA DLEU1 in OSCC. OSCC cell lines and human oral keratinocytes (HOKs) were cultured, while SCC-25 and CAL-27 cells were transfected with the corresponding plasmids. Reverse transcription quantitative PCR (RT-qPCR) and western blot were carried out to measure the RNA and protein levels. Cell proliferation, migration and invasion were evaluated using MTT assays, wound healing and Transwell assays. The StarBase database predicted the interactions between DLEU1 and miR-126-5p, as well as miR-126-5p and GAB1, which were further validated using a dual-luciferase reporter assay. Our results indicated that DLEU1 and GAB1 were upregulated, while miR-126-5p was downregulated in OSCC cells. Silencing DLEU1 reduced OSCC cell proliferation, migration, and invasion, while DLEU1 overexpression had the opposite effects. DLEU1 mediated biological effects in OSCC through binding to miR-126-5p, which directly targeted GAB1. miR-126-5p knockdown rescued the inhibitory function of DLEU1 depletion on proliferation, migration and invasion. Meanwhile, the miR-126-5p mimic exerted suppressive functions in the progression of OSCC, which were neutralized after GAB1 overexpression. In summary, lncRNA DLEU1 targets the miR-126-5p/GAB1 axis to aggravate OSCC progression, providing a novel target for treating OSCC.

[Effect of grape seed extract on oxidative stress and pathological changes of aorta in rats with chronic periodontitis and arteriosclerosis].

PURPOSE: To investigate the effect of grape seed extract on pathological changes of aorta in rats with chronic periodontitis and arteriosclerosis, and to analyze the possible mechanism. METHODS: Fifteen SPF male rats with chronic periodontitis and arteriosclerosis were randomly divided into three groups, i.e., model group(n=5), low dose of grape seed extract group (n=5), high dose of grape seed extract group (n=5) , and control group (n=10). The rats in the low and high dose groups were treated with 40 mg·kg-1·d-1 and 80 mg·kg-1·d-1 for 4 weeks respectively, while the rats in the normal control group and the model group were treated with the same amount of normal saline at the same time. The maximal intima-media thickness(IMT) of abdominal aorta was measured by H-E staining, the activity of SOD and the content of MDA in serum were measured by colorimetry, the content of GSH-px in serum and serum levels of inflammatory factor (TNF-α) and interleukin-6(IL-6) were detected by ELISA. p38 mitogen-activated protein kinase/nuclear transcription factor Kappa B p65(p38 MAPK/NF-κB p65) pathway was detected by Western blotting. SPSS 20.0 software package was used for statistical analysis. RESULTS: In the model group, the intima of abdominal aorta was irregularly thickened, with a lot of inflammatory cell infiltration, and arterial lesions appeared. In the low-and high-dose groups of grape seed extract, the plaque of abdominal aorta intima decreased and inflammatory cells reduced significantly, arterial vascular disease was improved, and the improvement was more obvious in high dose group than in low dose group. Compared with the control group, the levels of IMT, serum MDA, TNF-α, IL-6, p-p38MAPK/p38MAPK, NF-κB p65 and serum SOD and GSH-px in the model group were increased, while those in the model group were decreased(P＜0.05); the levels of IMT, serum MDA, TNF-α, IL-6, p-p38MAPK/p38MAPK, NF-κB p65 and SOD, GSH-px were decreased in the low and high dose groups(P＜0.05). CONCLUSIONS: Grape seed extract can inhibit the oxidative stress level and inflammatory reaction in serum of chronic periodontitis with arteriosclerosis rats, thus improving the intimal lesion of aorta, possibly by inhibiting the activation of p38MAPK/NF-κB p65 pathway.