LAUSR

Non‐small cell lung cancer (NSCLC) is the main histological subtype of lung cancer with a high incidence and mortality. Circular RNAs (circRNAs) exert vital functions in various cancers by acting as a sponge of miRNAs to abolish their inhibitory effect on target genes. This study aims to explore the biological function of circRNA NEDD4 binding protein 2 like 2 (circ‐N4BP2L2) in NSCLC. We found that circ‐N4BP2L2 was upregulated in NSCLC tissues and cells by using RT‐qPCR. A549 cells were transfected with pcDNA‐circN4BP2L2 or sh‐circN4BP2L2 to obtain circN4BP2L2‐overexpressed or ‐silenced cells, and then cell proliferation, invasion and apoptosis were determined. The results showed that knockdown of circ‐N4BP2L2 repressed cell proliferation, invasion as well as mitochondrial function, and promoted cell apoptosis; while overexpression of circ‐N4BP2L2 resulted in the opposite results. Mechanistically, the targeting correlations between miR‐135a‐5p and circ‐N4BP2L2 or ADP‐ribosylation factorlike 5B (ARL5B) were confirmed by using dual luciferase reporter, RNA pull‐down and RNA immunoprecipitation assays. In addition, we found that circ‐N4BP2L2 could promote the expression of ARL5B by serving as a sponge of miR‐135a‐5p. Moreover, rescue assays revealed that silencing miR‐135a‐5p or overexpressing ARL5B was able to abate the effects of circ‐N4BP2L2 knockdown on malignant phenotypes and mitochondrial function of A549 cells. Finally, tumorigenicity assay demonstrated that circ‐N4BP2L2 facilitated NSCLC tumor growth in vivo. Taken together, circ‐N4BP2L2 enhanced NSCLC progression via the miR‐135a‐5p/ARL5B axis, which may provide a novel therapeutic target of NSCLC.