Oral cancer is one of the common cancers worldwide, among which over 90% are oral squamous cell carcinomas (OSCC). MicroRNAs act as critical regulators of cancer development and progression. MiR-103a-3p has been reported to be upregulated in OSCC patients and closely correlated to poor prognosis, yet its roles in the progression of OSCC remain undisclosed. In this study, we knocked down the expression of miR-103a-3p in two OSCC cell lines in vitro, and significantly repressed cell proliferation and cell cycle arrest at the G1 phase were observed, accompanied by decreased proliferating cell nuclear antigen, cyclin D1, cyclin B1 and increased PTEN levels. MiR-103a-3p inhibition also induced apoptosis as evidenced by increased apoptotic cells and upregulated cleaved caspase-9/casapase-3 expression. We established a xenograft model in nude mice and found that miR-103a-3p knockdown also suppressed tumor growth in vivo. Besides, the expression of regulator of calcineurin1 (RCAN1), known as its anti-tumor effect, was negatively correlated with the miR-103a-3p level in OSCC cells. We validated that RCAN1 was a downstream target of miR-103a-3p using the dual-luciferase assay. RCAN1 silencing reversed the cell proliferative inhibition, cell cycle arrest and cell apoptosis induced by miR-103a-3p knockdown. In addition, we found that long non-coding RNA LINC00675 acted as a sponge of miR-103a-3p and promoted the expression of miR-103a-3p targets RCAN1 and PTEN. In summary, miR-103a-3p inhibition represses proliferation and induces apoptosis of OSCC cells through regulating RCAN1, and miR-103a-3p may act as a novel diagnostic marker and therapeutic target for OSCC.
BackgroundBehçet's disease (BD) is a chronic inflammatory disease affecting various size of arteries and veins. Coronary artery disease (CAD), a life-threatening condition, is rarely reported in patients BD.ObjectivesTo investigate the clinical characteristics of BD patients complicated with CAD, and to elucidate the potential risk factors of CAD in BD patients.MethodsWe retrospectively reviewed all the medical records of BD patients who were admitted to our institute from 2001 to 2016. CAD was defined as aneurysm, stenosis and (or) occlusion of coronary arteries confirmed by angiography or contrast-enhanced computer tomography. BD patients with CAD and age- and gender-matched BD patients without CAD (at 1:3 ratio) were enrolled. Demographic, clinical and laboratory data were systemically collected, analyzed and compared between two groups.ResultsIn total, 19 patients, including 17 male and 2 female, were complicated with CAD. The mean onset age of BD was 34 and the mean duration from the onset of BD to the diagnosis of CAD was 4.1 year. Angina pectoris (8/19) and acute myocardial infarction (8/19) were the most common cardiac symptoms, arrhythmia was presented in one patient, and three patient remained asymptomatic. Coronary artery aneurysm, stenosis and occlusion were presented in 9, 13 and 3 patients, respectively. Smoking (7/19) was frequently observed, while hypertension (3/16), diabetes mellitus (2/19), obesity (1/19) and alcohol consumption (1/19) were rarely present. Additionally, seven arterial and two venous extra-cardiac vasculopathies were presented. Oral ulceration (19/19) and skin lesions (16/19) were the most common BD-associated symptoms. Comparing with BD patients without CAD, patients with BD presented with higher ESR (mean, 34.4 vs 16.3 mm/hr, p=0.0018) and CRP (mean, 36.4 vs 12.2 mg/L, p=0.002), more frequency of skin lesions (84% vs 55%, p=0.0334) and pathergy reactions (37% vs 26%, p=0.0103). Furthermore, multivariate analysis confirmed that elevated CRP was a independent risk factor of CAD (OR 1.032, 95% CI 1.011–1.053, p=0.003).ConclusionsCAD, a rare complication of BD, predominately affect male patients. BD patients with CAD presented with active BD disease symptoms and elevated inflammatory markers, which implicated aberrant vascular inflammation was the key mechanism of CAD in BD patients. CRP, but not traditional CAD risk factors, was the risk factor of CAD in BD patients.Disclosure of InterestNone declared
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