CircRASSF2 promotes laryngeal squamous cell carcinoma progression by regulating the miR-302b-3p/IGF-1R axis

• Published in: Clinical science (1979) Vol. 133; no. 9; pp. 1053 - 1066
• Main Authors: Tian, Linli, Cao, Jing, Jiao, Hui, Zhang, Jiarui, Ren, Xiuxia, Liu, Xinyu, Liu, Ming, Sun, Yanan
• Format: Journal Article
• Language: English
• Published: England 15.05.2019
• Subjects: Carcinoma, Squamous Cell - genetics; Cell Line, Tumor; Cell Proliferation - genetics; Down-Regulation; Gene Expression Regulation, Neoplastic - genetics; Humans; Laryngeal Neoplasms - genetics; MicroRNAs - genetics; Receptor, IGF Type 1 - genetics; Tumor Suppressor Proteins - genetics; Up-Regulation; miR-302b-3p; LSCC; IGF-1R; ceRNAs; circRASSF2; exosome
• ISSN: 0143-5221; 1470-8736
• DOI: 10.1042/CS20190110

Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with laryngeal squamous cell carcinoma (LSCC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for LSCC from the aspect of circRNA-microRNA (miRNA)-mRNA interaction. We investigated the expression of circRNAs in three paired LSCC tissues and adjacent non-tumor tissues by microarray analysis. Differentially expressed circRNAs were identified between LSCC tissues and non-cancerous matched tissues, including 527 up-regulated circRNAs and 414 down-regulated circRNAs. We focused on hsa_circ_0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2. circRASSF2 was found to be significantly up-regulated in LSCC tissues and LSCC cell lines compared with paired adjacent non-tumorous tissues and normal cells. Moreover, knockdown of circRASSF2 significantly inhibited cell proliferation and migration , which was blocked by miR-302b-3p inhibitor. Bioinformatics analysis predicted that there is a circRASSF2/miR-302b-3p/ insulin-like growth factor 1 receptor (IGF-1R) axis in LSCC progression. Dual-luciferase reporter system validated the direct interaction of circRASSF2, miR-302b-3p, and IGF-1R. Western blot verified that inhibition of circRASSF2 decreased IGF-1R expression. Furthermore, silencing circRASSF2 suppressed LSCC growth Importantly, we demonstrated that circRASSF2 was up-regulated in serum exosomes from LSCC patients. Altogether, silencing circRASSF2 suppresses progression of LSCC by interacting with miR-302b-3p and decreasing inhibiting IGF-1R expression. In conclusion, these data suggest that circRASSF2 is a central component linking circRNAs to progression of LSCC via an miR-302b-3p/IGF-1R axis.