Biomedicine & Pharmacotherapy (May 2020)
Overexpression of circRNA_100290 promotes the progression of laryngeal squamous cell carcinoma through the miR-136-5p/RAP2C axis
Abstract
Circular RNAs (circRNAs) exert critical functions in tumorigenesis and tumor development, but whether and how circRNAs contribute to laryngeal squamous cell carcinoma (LSCC) is unclear. In this study, we explored the function and mechanisms of circRNA_100290 in LSCC. Tissue samples were obtained from 40 patients with LSCC. The expression of circRNA_100290 and other targets was measured through quantitative reverse transcription-polymerase chain reaction and western blot analysis. Cell proliferation, colony-forming ability, and apoptosis were tested using CCK-8 assay and EdU assay, colony formation assay, and flow cytometry, respectively. Cell migration and invasion were detected by Transwell assay. Moreover, the interactions between circRNA_100290, miR-136-5p, and RAP2C were analyzed by bioinformatics, and verified by dual‐luciferase reporter assays. Here, we found that circRNA_100290 expression was significantly upregulated in LSCC tissues and cell lines compared with the normal controls. Expression of circRNA_100290 positively correlated with advanced TNM stage and lymph node metastasis in LSCC patients. In cell culture, upregulation of circRNA_100290 promoted LSCC cell proliferation, migration, and invasion, while it inhibited cell apoptosis; downregulating circRNA_100290 exerted the opposite effects. In vivo, circRNA_100290 overexpression dramatically promoted tumor growth. Mechanistically, circRNA_100290 may act as a sponge of miR-136-5p, and inhibiting miR-136-5p in LSCC cells indeed reversed the effects of circRNA_100290 downregulation. The RAS oncogene RAP2C was predicted to be a target of miR-136-5p, and downregulating RAP2C in LSCC cells partially reversed the oncogenic effects of circRNA_100290 overexpression or miR-136-5p decrease. Our findings suggest that circRNA_100290 promotes LSCC progression by targeting the miR-136-5p/RAP2C axis, which may lead to the identification of potential therapeutic targets.
