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

Abstract

Background: Circular 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.

Methods: Quantitative 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.

Results: Circ_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.

Conclusions: Circ_PLXND1 knockdown impeded NSCLC progression through modulating the miR-1287-5p/ERBB3 axis, indicating a promising molecular target for NSCLC treatment.

Keywords: ERBB3; NSCLC; circ_PLXND1; miR-1287-5p.