Circ-EIF3I facilitates proliferation, migration, and invasion of lung cancer via regulating the activity of Wnt/β-catenin pathway through the miR-1253/NOVA2 axis.

Abstract

Many studies have shown that circular RNA (circRNA) is an important regulator mediating the malignant progression of cancer. However, the role and mechanism of circ-EIF3I in lung cancer (LC) development are still unclear. A total 36 paired LC tumor tissues and adjacent normal tissues were enrolled. The expression of circ-EIF3I, microRNA (miR)-1253, and neuro-oncological ventral antigen 2 (NOVA2) was measured by quantitative real-time PCR. The proliferation, apoptosis, migration, and invasion of LC cells were determined by MTT assay, colony formation assay, flow cytometry, and transwell assay. Dual-luciferase reporter assay was performed to verify the interaction between miR-1253 and circ-EIF3I or NOVA2. The protein levels of NOVA2 and Wnt/β-catenin pathway-related markers were detected by western blot analysis. Xenograft tumor was constructed to explore the function of circ-EIF3I on LC tumor growth. Circ-EIF3I was upregulated in LC tumor tissues and cells. Silenced circ-EIF3I could suppress the proliferation, migration, invasion, and enhance the apoptosis of LC cells in vitro, as well as reduce LC tumor growth in vivo. Circ-EIF3I could sponge miR-1253, and miR-1253 inhibitor overturned the regulation of circ-EIF3I knockdown on LC cell progression. NOVA2 was confirmed to be a target of miR-1253, which could reverse the inhibitory effects of miR-1253 on LC cell progression. Further experiments showed that circ-EIF3I regulated NOVA2 expression by sponging miR-1253. In addition, circ-EIF3I silencing could inhibit the activity of Wnt/β-catenin pathway via regulating the miR-1253/NOVA2 axis. Circ-EIF3I might function as an oncogene in LC, which promoted LC progression by the miR-1253/NOVA2/Wnt/β-catenin network.