Knockdown of circADAM9 inhibits cell progression and glycolysis by targeting the miR‐1236‐3p/FGF7 axis in breast cancer

Abstract

AbstractBackgroundCircular RNAs (circRNAs) are closely associated with the development of breast cancer (BC). In this study, we aimed to clarify how differentially expressed circRNAs affect the development of BC.MethodsQuantitative real‐time polymerase chain reaction (qRT‐PCR) was used to detect the expression of circADAM9, miR‐1236‐3p and fibroblast growth factor 7 (FGF7). Colony formation, 5‐ethynyl‐2′‐deoxyuridine (EdU), wound healing, transwell, and flow cytometry were used to assess cell proliferation, migration, invasion, and apoptosis. Glucose consumption, lactic acid production and ATP levels were assessed using glycolysis metabolism analysis. Dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to verify the relationship between miR‐1236‐3p and circADAM9 or FGF7. The roles of cirADAM9 on tumor growth were analyzed using a xenograft tumor model. Ki‐67 and FGF7 expression was measured via immunohistochemistry (IHC) assay. Apoptosis‐related proteins and exosome markers were detected by western blot.ResultsCircADAM9 was highly expressed in BC cells, and circADAM9 silencing inhibited BC cell proliferation, migration, invasion, and glycolysis, and promoted cell apoptosis. Furthermore, miR‐1236‐3p inhibition could overturn circADAM9 knockdown‐mediated BC inhibition. Moreover, the negative influences of miR‐1236‐3p overexpression on BC progression were restrained via FGF7 overexpression. CircADAM9 silence also inhibited BC tumor growth in vivo.ConclusionCircADAM9 promoted BC development partly by the miR‐1236‐3p/FGF7 axis, highlighting a potential prognostic biomarker and therapeutic target for BC patients.