Circ‐PDZD8 promotes cell growth and glutamine metabolism in non‐small cell lung cancer by enriching LARP1 via sequestering miR‐330‐5p

Abstract

AbstractBackgroundThe deregulation of circular RNA (circRNA) is widely reported in carcinogenesis. The purpose of this study was to investigate the role of circRNA‐PDZ domain containing 8 (circ‐PDZD8) in non‐small cell lung cancer (NSCLC) progression.MethodsThe histological structure of tissues was identified by hematoxylin–eosin (HE) staining analysis. The expression levels of circ‐PDZD8, miR‐330‐5p and la ribonucleoprotein 1 (LARP1) mRNA were ascertained by qPCR. Cell counting kit‐8, colony formation, flow cytometry, and transwell assays were employed for functional analysis. Glutamine metabolism was monitored by glutamine consumption, alpha ketoglutarate (α‐KG) level and adenosine triphosphate (ATP) level. A xenograft model was established to ascertain the role of circ‐PDZD8 in vivo. The putative binding relationships were verified by dual‐luciferase and RIP studies.ResultsCirc‐PDZD8 expression was highly increased in NSCLC. Circ‐PDZD8 knockdown inhibited cell growth, migratory capacity, invasiveness and glutamine metabolism but enhanced cell apoptosis in NSCLC cells. Circ‐PDZD8 blocked miR‐330‐5p expression, and miR‐330‐5p inhibition overturned the effects of circ‐PDZD8 absence. LARP1 targeted by miR‐330‐5p, and miR‐330‐5p upregulation‐impaired cell growth, motility and glutamine metabolism were recovered by LARP1 overexpression. Circ‐PDZD8 knockdown was also shown to impede solid tumor growth.ConclusionCirc‐PDZD8 promotes NSCLC cell growth and glutamine metabolism by increasing LARP1 via competitively targeting miR‐330‐5p.