The FASEB Journal · 2022 · 13 citations · 23 references
MedicineCancer BiologyOncologyGene ExpressionMolecular OncologyTumor ProgressionCancer Cell SignalingCancer ProgressionGastric CancerMicrorna-mediated RegulationSignal Transduction In CancerTumor Suppressor GenesLuciferase Reporter AssaysMicrorna Function In CancerMicrorna In CancerMicrorna Regulation In CancerMicrorna-mediated OncogenesisQuantitative Reporter AssaysRescueTumor Growth Dynamics
Circular RNAs participate in the pathogenesis of various tumors, including gastric cancer (GC). In this study, we investigated the role of circBGN in regulating proliferation and invasion of GC cells and elucidated the mechanism. The expression of circBGN was assessed by quantitative reverse-transcription PCR and in situ hybridization. In addition, loss- and gain-of-function investigations in vitro and in vivo were performed to determine the biological functions of circBGN. Luciferase reporter assays and rescue experiments were applied to investigate the interaction between circBGN and miR-149-5p as well as the relationship between miR-149-5p and IL6. Our results showed that circBGN expression was significantly elevated in GC tissues and cells. Knockdown of circBGN dramatically suppressed GC cell proliferation and invasion in vitro. Xenograft experiments revealed that knockdown of circBGN delayed tumor growth in vivo. Furthermore, circBGN can directly bind to miR-149-5p, thereby preventing miR-149-5p from binding to its target mRNA [IL6 mRNA], thus activating IL6/STAT3 signaling pathway. Rescue assays indicated that circBGN regulates GC cell proliferation and invasion by upregulating miR-149-5p/IL6 axis output. Taken together, our investigation indicates that circBGN supports GC progression by activating IL6/STAT3 signaling pathway, thus pointing to a new possible therapeutic target in GC.
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Rebecca L. Siegel, Kimberly D. Miller, Hannah E. Fuchs et al. · CA A Cancer Journal for Clinicians · 2021 · 17.4K citations · Full text