CircRUNX1 drives the malignant phenotypes of lung adenocarcinoma through mediating the miR-5195-3p/HMGB3 network.

Abstract

Circular RNAs (circRNAs) are key factors in the regulation of cancer progression. However, the role of circRUNX1 in lung adenocarcinoma (LUAD) progression is unclear. The expression levels of circRUNX1, microRNA (miR)-5195-3p, and high-mobility group protein B3 (HMGB3) were detected by quantitative real-time PCR. Cell proliferation, migration, invasion and apoptosis were analyzed by EdU staining, colony formation assay, transwell assay and flow cytometry. Protein levels were measured using western blot analysis. The interaction between miR-5195-3p and circRUNX1 or HMGB3 was verified by dual-luciferase reporter assay and RIP assay. Animal experiments were performed to investigate the role of circRUNX1 in LUAD tumorigenesis. We found that circRUNX1 was upregulated in LUAD tumor tissues and cells. CircRUNX1 knockdown suppressed LUAD cell proliferation and metastasis, while promoted apoptosis. In terms of mechanism, we found that circRUNX1 could sponge miR-5195-3p, and miR-5195-3p inhibitor abolished the regulation of circRUNX1 knockdown on LUAD cell proliferation, metastasis and apoptosis. In addition, miR-5195-3p could target HMGB3, and HMGB3 overexpression reversed the inhibition effect of miR-5195-3p on LUAD progression. Moreover, circRUNX1 knockdown reduced LUAD tumorigenesis. CircRUNX1 facilitated LUAD proliferation and metastasis by regulating the miR-5195-3p/HMGB3 axis, suggesting that it might be a possible therapeutic target for LUAD.