CiRS-7 functions as a ceRNA of RAF-1/PIK3CD to promote metastatic progression of oral squamous cell carcinoma via MAPK/AKT signaling pathways

• Published in: Experimental cell research 2020-11, Vol.396 (2), p.112290, Article 112290
• Main Authors: Dou, Zhichao, Gao, Ling, Ren, Wenhao, Zhang, Hao, Wang, Xiaofei, Li, Shaoming, Zheng, Jingjing, Kong, Xinjuan, Chi, Peng, Zhi, Keqian
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Carcinogenesis - pathology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; ciRS-7; Class I Phosphatidylinositol 3-Kinases - metabolism; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Male; MAP Kinase Signaling System; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; miR-7; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Neoplasm Invasiveness; Neoplasm Metastasis; Oral squamous cell carcinoma; PIK3CD; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-raf - metabolism; RAF-1; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Up-Regulation - genetics
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2020.112290

Recent findings have shown that circRNA dysregulation was involved in the development of many types of cancer. However, our knowledge of circRNA in oral squamous cell carcinoma (OSCC) remains elusive. Here, we explored whether ciRS-7 could function as a ceRNA in promoting metastasis of OSCC via regulating miR-7 activity. The expression levels of ciRS-7 and miR-7 were examined in clinical samples and cell lines by qRT-PCR, and the effects of ectopic expression of ciRS-7 and miR-7 on cell proliferation, migration and invasion were assessed in vitro and in vivo. The effects of ciRS-7 on miR-7 activity were investigated by means of luciferase reporter assay, qRT-PCR and Western blot. In addition, the effects of miR-7 mediated ciRS-7 on the levels of MAPK/AKT signaling proteins were evaluated by Western blot. We found that ciRS-7 was highly expressed in OSCC tissues and cell lines compared with normal counterparts. Ectopic expression of ciRS-7 significantly promoted OSCC cell proliferation, migration and invasion through in vitro and in vivo. Based on bioinformatics analysis, qRT-PCR, Western blot and luciferase reporter assays, we determined that ciRS-7 functioned as a sponge for miR-7, resulting in attenuation of miR-7 targets RAF-1 and PIK3CD, which are core components of the MAPK/AKT signaling pathways. Moreover, miR-7 correlated with perineural and lymphovascular invasion in OSCC patients. Further experiments demonstrated that ciRS-7 overexpression could attenuate the anti-tumor effects of miR-7 on OSCC cells. Our results suggested that ciRS-7 can interact directly with miR-7, resulting in upregulation of RAF-1/PIK3CD expression and enhancing metastatic progression of OSCC.