Background: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, with a poor prognosis. The roles of circular RNAs (circRNAs) in tumors have been initially clarified. In this study, we probed into the functions and underlying molecular mechanisms of circ-ANXA7 in LUAD.
Methods: According to circRNA microarray analysis based on 40 pairs of LUAD tissues and non-tumor tissues, a novel circ-ANXA7 was up-regulated in LUAD, which was verified in LUAD tissues and cells by RT-qPCR. Correlation between its expression and clinical features of LUAD was analyzed. When transfected with sh-circ-ANXA7, proliferation, invasion, and migration of LUAD cells were determined by a series of functional assays. Furthermore, tumor growth was investigated in nude mice injected with sh-circ-ANXA7. Dual luciferase report and gain and loss assays were used to confirm the relationships between circ-ANXA7 and miR-331, miR-331 and LAD1.
Results: circ-ANXA7 was up-regulated in LUAD tissues and cells. Its high expression promoted proliferation, migration, and invasion of LUAD cells as well as tumor growth. High circ-ANXA7 expression usually predicted a poorer prognosis for LUAD patients. Furthermore, circ-ANXA7 could accelerate proliferation and invasion of LUAD cells by targeting miR-331. miR-331 directly bound to the 3'-UTR of LAD1. LAD1 induced proliferation and invasion of LUAD cells, which was reversed after co-transfection with circ-ANXA7 knockdown. LAD1 expression could be an independent prognostic marker for LUAD by univariate and multivariate analysis.
Conclusions: Our research identified a novel circ-ANXA7 for LUAD, which could facilitate proliferation, migration, and invasion of LUAD cells by miR-331/ LAD1 axis. circ-ANXA7 could become a promising prognosis and treatment target for LUAD.
Keywords: Invasion; LAD1; Lung adenocarcinoma; Proliferation; circ-ANXA7; miR-331.