Downregulation of circ_PLXND1 inhibits tumorigenesis of non‐small cell lung carcinoma via miR‐1287‐5p/ERBB3 axis

Abstract

AbstractBackgroundCircular RNAs (circRNAs) have been reported to play vital roles in the progression of diverse human cancers, including non‐small cell lung cancer (NSCLC). The purpose of this study was to explore the exact role and underlying mechanism of circ_PLXND1 in NSCLC progression.MethodsQuantitative real‐time polymerase chain reaction (qRT‐PCR) assay was performed to determine the expression levels of circ_PLXND1, microRNA (miR)‐1287‐5p and human epidermal growth factor receptor 3 (ERBB3). The localization of circ_PLXND1 in NSCLC cells was tested by subcellular fractionation and localization assay. Cell angiogenesis, proliferation, apoptosis, migration and invasion were evaluated by tube formation assay, 5‐ethynyl‐2′‐deoxyuridine (EdU) incorporation assay, 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide (MTT) assay, flow cytometry and transwell assay. Dual‐luciferase reporter assay was utilized to confirm the interaction between miR‐1287‐5p and circ_PLXND1 or ERBB3. Western blot assay was exploited to examine the expression of proteins.ResultsCirc_PLXND1 and ERBB3 were upregulated while miR‐1287‐5p was downregulated in NSCLC tissues and cells. Circ_PLXND1 was a stable circRNA and mainly located in cytoplasm. Circ_PLXND1 silencing suppressed the proliferation, angiogenesis, migration and invasion of NSCLC cells in vitro. For mechanism analysis, circ_PLXND1 could positively regulate ERBB3 expression via sponging miR‐1287‐5p. The inhibitory impacts of circ_PLXND1 knockdown on the malignant behaviors of NSCLC cells were overturned by miR‐1287‐5p inhibitor. Overexpression of miR‐1287‐5p repressed the malignant phenotypes of NSCLC cells by targeting ERBB3. Furthermore, circ_PLXND1 interference inhibited tumor growth in vivo.ConclusionsCirc_PLXND1 knockdown impeded NSCLC progression through modulating the miR‐1287‐5p/ERBB3 axis, indicating a promising molecular target for NSCLC treatment.