Circular RNA circ_0006948 Promotes Esophageal Squamous Cell Carcinoma Progression by Regulating microRNA-3612/LASP1 Axis

Abstract

Esophageal squamous cell carcinoma (ESCC) is the most prevalent malignancy worldwide. Circular RNAs (circRNAs) circ_0006948 is reported to be upregulated in ESCC cells. This study is designed to explore the role and mechanism of circ_0006948 in ESCC progression. Circ_0006948, linear FNDC3B, microRNA-3612 (miR-3612), and LIM and SH3 protein 1 (LASP1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, colony number, migration, invasion, and apoptosis were examined by Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays, severally. Glucose consumption, lactate production, and ATP level were measured by the corresponding kits. Protein levels of hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), and LASP1 were assessed by western blot assay. The cytoplasmic localization of circ_0006948 was identified by the subcellular fractionation assay. The binding relationship between miR-3612 and circ_0006948 or LASP1 was predicted by starBase or TargetScan and then verified by a dual-luciferase reporter assay. The biological role of circ_0006948 on ESCC tumor growth was examined by the xenograft tumor model in vivo. Circ_0006948 and LASP1 were increased, and miR-3612 was decreased in ESCC tissues and cells. Furthermore, circ_0006948 knockdown could suppress cell viability, colony number, migration, invasion, glycolysis, and boost apoptosis in ESCC cells. Mechanically, circ_0006948 could act as a sponge of miR-3612 to regulate LASP1 expression. In addition, circ_0006948 silencing inhibited ESCC tumor growth in vivo. Circ_0006948 boosted ESCC progression partly by regulating the miR-3612/LASP1 axis, providing an underlying therapeutic target for the ESCC treatment.