Silencing of circ_0088036 inhibits growth and invasion of lung adenocarcinoma through miR‐203/SP1 axis

Abstract

AbstractLung cancer is the leading cause of cancer‐related deaths worldwide. Circular RNA (circRNA) circ_0088036 is a recently discovered circRNA known for its roles in rheumatoid arthritis. The study aimed to study the function of circ_0088036 in lung adenocarcinoma (LUAD). Circ_0088036 expressions were analyzed in the Gene Expression Omnibus (GEO) database. The relationship between circ_0088036 expressions and clinicopathological data of LUAD was assessed. The messenger RNA and protein levels were analyzed by quantitative real‐time polymerase chain reaction and Western blot. Cell viability, apoptosis, and invasion were tested by Cell Counting Kit‐8, flow cytometry, and transwell assay. The direct interaction between microRNA‐203 (miR‐203) and circ_0088036 or specificity protein 1 (SP1) was confirmed by dual‐luciferase reporter assay, RNA pull‐down, and RNA immunoprecipitation assays. Circ_0088036 was overexpressed in LUAD from the analysis of the GEO database. The poor prognosis was found in the patients with high expressions of circ_0088036. The level of Circ_0088036 was increased in LUAD tissues and cells. In terms of function, the deletion of circ_0088036 inhibited LUAD tumorigenesis in vitro by repressing cell growth, invasion, and epithelial–mesenchymal transition (EMT). In mechanism, circ_0088036 could competitively sponge miR‐203, thereby affecting the expressions of the target gene SP1. In addition, lessening of miR‐203 and enlarging of SP1 could eliminate the anticancer effect of short hairpin RNA‐circ_0088036 on LUAD cells. Besides, the knockout of circ_0088036 hindered the growth of xenografted tumors in vivo. Circ_0088036 promoted the LUAD cell growth, invasion, and EMT via modulating the miR‐203/SP1 axis in LUAD.