CircRNA SOD2 motivates non-small cell lungs cancer advancement with EMT via acting as microRNA-2355-5p’s competing endogenous RNA to mediate calmodulin regulated spectrin associated proteins-2

Circular RNAs (circRNAs) are closely linked with human cancer development such as non-small-cell lung cancer (NSCLC). However, the characteristics and specific functions of most circRNAs in NSCLC remained unknown. Previous studies have suggested that circRNA SOD2 (CircSOD2) expression was upregulated in a number of cancers. This study aimed to explore the functions of circSOD2 in NSCLC advancement with epithelial-mesenchymal transition (EMT). Expression profile analysis of circSOD2, miR-2355-5p, and calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) was detected by real-time quantitative PCR (RT-qPCR). Transwell assay, cell migration assay, CCK8, ELISA, RIP assay, RNA pull-down assay, and Western blot analysis were performed to evaluate the functions of circSOD2, miR-2355-5p, and CAMSAP2. We found elevated expression of circSOD2 and CAMSAP2 while reduced expression of miR-2355-5p in NSCLC tumor tissues. Silencing or overexpression of CircSOD2 resulted in increased or decreased expression of miR-2355-5p, respectively. Mechanically, we showed that silencing of CircSOD2 and overexpression of miR-2355-5p resulted in the reduced rate of NSCLC cell proliferation. Inhibition of miR-2355-5p reversed the changes induced via silencing of CircSOD2. MiR-2355-5p binds to the CircSOD2 promoter and triggered its stimulation, which further activated circSOD2 expression. CircSOD2 suppression impaired lung cancer cell growth, cell migration, prohibited cell cycle progression, and in vivo tumor growth by targeting miR-2355-5p expression in NSCLC tissues. Meanwhile, increased expression of CAMSAP2 reversed the changes stimulated by the elevated level of miR-2355-5p in NSCLC progression. This innovative signaling axis CircSOD2/miR-2355-5p/CAMSAP2 illustrated the new horizon to investigate NSCLC tumorigenesis and provided new prognosis and treatment of NSCLC.