Circular RNAs are frequently dysregulated and show important regulatory function of tumorigenesis in cancers. Hsa_circ_0007380 was found to be elevated in human radioresistant esophageal cancer cells. Here, this study aimed to investigate the action and mechanism of hsa_ circ_0007380 in esophageal cancer carcinogenesis and radiosensitivity. Quantitative real-time PCR and western blotting were performed to detect levels of genes and proteins. Functional experiments were conducted using MTT assay, EdU assay, clonogenic survival assay, flow cytometry and murine xenograft model assay, respectively. The binding between miR-644a and hsa_circ_0007380 or spindlin1 (SPIN1) was validated using dual-luciferase activity assay. Hsa_circ_0007380 was highly expressed in esophagus cancer tissues and cells, knockdown of hsa_circ_0007380 suppressed esophagus cancer cell proliferation, induced apoptosis and enhanced radiosensitivity in vitro, and the same effects were also confirmed in nude mice. Mechanistically, hsa_ circ_0007380 sequestered miR-644a to release SPIN1 expression, implying the hsa_circ_0007380/miR-644a/ SPIN1 competing endogenous RNA network esophagus cancer cells. miR-644a was decreased in esophagus cancer, re-expression of miR-644a restrained cell growth and conferred radiosensitivity in esophagus cancer, which were reversed by SPIN1 overexpression. Besides that, inhibition of miR-644a abolished the promoting action of hsa_circ_0007380 knockdown on esophagus cancer apoptosis and radiosensitivity. Hsa_circ_0007380 silencing impedes cell growth and reinforces radiosensitivity in esophagus cancer by miR-644a/SPIN1 axis, suggesting a promising therapeutic target for esophagus cancer combined treatment.
Radioresistance is one of main causes of treatment failure in esophageal squamous cell carcinoma (ESCC). Circular RNAs (circRNAs) exhibit significant regulation in radiosensitivity of cancers. This paper focused on the function of circRNA PTPRF interacting protein alpha 1 (circPPFIA1) in radiosensitivity of ESCC. Levels of circPPFIA1, microRNA‐1299 (miR‐1299) and thioredoxin reductase 1 (TXNRD1) were examined using reverse transcription‐quantitative polymerase chain reaction assay. Flow cytometry was applied for assessment of cell apoptosis. The protein expression was measured through western blot. Survival fraction was detected by colony formation assay. Target binding was identified via dual‐luciferase reporter assay and RNA immunoprecipitation assay. In vivo research was performed by xenograft tumor assay. Radiation treatment induced circPPFIA1 upregulation in ESCC cells. Radiosensitivity was enhanced in ESCC cells after downregulation of circPPFIA1. MiR‐1299 was a target of circPPFIA1. The regulatory function of circPPFIA1 knockdown in radiosensitivity was achieved by upregulating miR‐1299. CircPPFIA1 affected TXNRD1 expression via targeting miR‐1299. Overexpression of miR‐1299 promoted radiosensitivity in ESCC cells by downregulating TXNRD1. Radiosensitivity in vivo was also elevated by silence of circPPFIA1 via regulating miR‐1299 and TXNRD1 levels. All experimental data showed that knockdown of circPPFIA1 contributed to radiosensitivity in ESCC by inducing miR‐1299‐related downregulation of TXNRD1.
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