Abstract
BackgroundThe implication of circular RNAs (circRNAs) in human cancers has aroused much concern. In this study, we investigated the function of circ_0000745 and its potential functional mechanisms in oral squamous cell carcinoma (OSCC) to further understand OSCC pathogenesis.MethodsThe expression of circ_0000745, miR-488 and cyclin D1 (CCND1) mRNA was measured by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation capacity was assessed by cell counting kit-8 (CCK-8) assay and colony formation assay. Cell cycle progression and cell apoptosis were determined by flow cytometry assay. The protein levels of CCND1, PCNA, Cleaved-caspase 3 and HuR were detected by western blot. Animal study was conducted to identify the role of circ_0000745 in vivo. The targeted relationship was verified by dual-luciferase reporter assay, pull-down assay or RNA immunoprecipitation (RIP) assay.ResultsThe expression of circ_0000745 was increased in OSCC tissues and cells. Circ_0000745 downregulation inhibited OSCC cell proliferation and induced cell cycle arrest and apoptosis in vitro, as well as blocked tumor growth in vivo. MiR-488 was a target of circ_0000745, and circ_0000745 downregulation suppressed OSCC development by enriching miR-488. Besides, circ_0000745 regulated CCND1 expression by targeting miR-488. In addition, circ_0000745 regulated CCND1 expression by interacting with HuR protein. CCND1 knockdown also inhibited OSCC cell proliferation and induced cell cycle arrest and apoptosis in vitro, and CCND1 overexpression recovered the inhibitory effects on OSCC cell malignant behaviors caused by circ_0000745 downregulation.ConclusionsCirc_0000745 regulated the expression of CCND1 partly by acting as miR-488 sponge and interacting with HuR protein, thus promoting the progression of OSCC.
Highlights
Oral squamous cell carcinoma (OSCC), the most common type of oral cancer, is stated to be the sixth to eighth most common cancer worldwide [1]
To determine the role of circ_0000745 in oral squamous cell carcinoma (OSCC), we investigated its expression in OSCC tissues and cells and explored its function on OSCC cell growth and apoptosis in vitro as well as tumor growth in vivo
In cell counting kit-8 (CCK-8) assay, we found that Cal-27 and SCC9 cells with sh-circ_0000745#1 transfection decreased multiplication capacity (Fig. 2b)
Summary
Oral squamous cell carcinoma (OSCC), the most common type of oral cancer, is stated to be the sixth to eighth most common cancer worldwide [1]. It occurs anywhere in the mouth, including the tongue, upper and lower gums, palate and buccal mucosa [2]. Despite advances in technology and treatment options, the survival rate of OSCC patients has not increased significantly (< 50 % in the last three decades) [1, 3]. With the progress of studies on OSCC pathogenesis, new molecular markers attract much attention, which can be used to predict the prognosis of patients and estimate the overall survival rate of different cancers. We investigated the function of circ_0000745 and its potential functional mechanisms in oral squamous cell carcinoma (OSCC) to further understand OSCC pathogenesis
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