Abstract
BackgroundIncreasing studies focused on the regulatory roles of circular RNAs (circRNAs) in diverse cancers. This study was to evaluate the function and mechanism of circRNA Scm-like with four malignant brain tumor domains 2 (circ-SFMBT2) in esophageal cancer (EC).MethodsThe circ-SFMBT2, microRNA-107 (miR-107) and solute-linked carrier family A1 member 5 (SLC1A5) levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay, colony formation assay and EdU assay. Cell apoptosis and invasion were detected by flow cytometry and transwell assay. Glutamine metabolism was assessed by the corresponding kits for glutamine consumption, α-ketoglutarate production and glutamate production. Western blot was used for protein quantification. The binding analysis was performed using dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and pull-down assays. The functional research of circ-SFMBT2 in vivo was performed by xenograft tumor assay. Exosomes were identified by morphological observation and protein detection.ResultsCirc-SFMBT2 was overexpressed in EC samples and cells. Circ-SFMBT2 downregulation inhibited EC cell proliferation, invasion and glutamine metabolism. Circ-SFMBT2 targeted miR-107 and the regulation of circ-SFMBT2 was achieved by sponging miR-107. SLC1A5 was a target of miR-107, and it worked as an oncogene in EC cells. MiR-107 retarded the EC progression by downregulating SLC1A5. Circ-SFMBT2 could affect the SLC1A5 expression by targeting miR-107. Circ-SFMBT2 regulated EC progression in vivo by miR-107/SLC1A5 axis. Circ-SFMBT2 was transferred by exosomes in EC cells.ConclusionThese results suggested that circ-SFMBT2 upregulated the SLC1A5 expression to promote the malignant development of EC by serving as a miR-107 sponge.
Highlights
Increasing studies focused on the regulatory roles of circular RNAs in diverse cancers
IHC analysis revealed that Ki67 protein level of tumor group was higher than that of normal group, showing that cell proliferation was promoted in esophageal cancer (EC) samples (Fig. 1B)
The survival curve indicated that the overall survival was decreased in EC patients with high expression of circ-SFMBT2 relative to the patients with low expression of circ-SFMBT2, suggesting that circSFMBT2 could be a prognostic target for EC patients (Fig. 1G)
Summary
Increasing studies focused on the regulatory roles of circular RNAs (circRNAs) in diverse cancers. This study was to evaluate the function and mechanism of circRNA Scm-like with four malignant brain tumor domains 2 (circ-SFMBT2) in esophageal cancer (EC). Circular RNAs (circRNAs) and microRNAs (miRNAs) are well-known subtypes of ncRNAs involving in cancer progression [5]. CircRNAs are endogenous and covalently closed RNAs with tissue/cell-specific expression patterns in eukaryotes [6]. CircRNA Scm-like with four malignant brain tumor domains 2 (circ-SFMBT2) has been shown to promote cell proliferation in gastric cancer by the miR182-5p/CREB1 axis [10]. GSE131969 dataset (https://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE131969) showed that circ-SFMBT2 was highly expressed in EC tissues. It is unknown about the biological role and mechanism of circ-SFMBT2 in EC
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