Circ_0016760 accelerates non‐small‐cell lung cancer progression through miR‐646/AKT3 signaling in vivo and in vitro

Abstract

Abstract Background Currently, the prognosis of non‐small‐cell lung cancer (NSCLC) patients remains dismal due to recurrence and metastasis. The purpose of our study was to explore the role of circular RNA_0016760 (circ_0016760) in NSCLC progression and its associated mechanism. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was implemented to measure the expression of circ_0016760, microRNA‐646 (miR‐646) and AK strain thymoma serine/threonine kinase 3 (AKT3). The protein level of AKT3 was examined by Western blot assay. Cell Counting Kit 8 assay, transwell assays, and flow cytometry were conducted to analyze cell proliferation, metastasis, and apoptosis. Dual‐luciferase reporter assay was used to confirm the interactions that were predicted by bioinformatics software (Circular RNA Interactome and TargetScan). A xenograft tumor model was built to investigate the role of circ_0016760 in vivo. Results Circ_0016760 and AKT3 were highly expressed in NSCLC tissue specimens and cell lines. Circ_0016760 interference suppressed cell proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. Circ_0016760 interacted with miR‐646 and negatively regulated its expression. MiR‐646 silencing partly counteracted circ_0016760 knockdown‐mediated influences in NSCLC cells. MiR‐646 bound to the AKT3 3′ untranslated region in NSCLC cells, and miR‐646 overexpression‐induced effects in NSCLC cells were partly overturned by the addition of AKT3 overexpression plasmid. Circ_0016760 silencing reduced the expression of AKT3 through enhancing miR‐646 expression. Circ_0016760 knockdown suppressed NSCLC tumor growth in vivo. Conclusion Circ_0016760 played an oncogenic role to promote the proliferation, migration, and invasion and restrained the apoptosis of NSCLC cells via miR‐646/AKT3 signaling.

Keywords

• AKT3
• circ_0016760
• miR‐646
• non‐small‐cell lung cancer