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

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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.

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