Exosome‐transported of circ_0081069 induces SPIN1 production by binding to miR‐195‐5p to inhibit radiosensitivity in esophageal squamous cell carcinoma

Abstract

AbstractCirc_0081069 plays a key role in tumor growth; however, its effect on radiosensitivity in esophageal squamous cell carcinoma (ESCC) remains unknown. The study is performed to reveal the association of circ_0081069 expression and radiosensitivity in ESCC and the underlying mechanism. Circ_0081069, miR‐195‐5p, and spindlin 1 (SPIN1) RNA expression were detected by quantitative real‐time polymerase chain reaction. Protein expression was checked by Western blot analysis or immunohistochemistry assay. Cell viability, proliferation, cell apoptosis, migration, and invasion were investigated by cell counting kit‐8, 5‐Ethynyl‐29‐deoxyuridine, flow cytometry analysis, scratch test, and transwell assays, respectively. The sensitivity of ESCC cells to radiation was investigated by cell colony formation assay. The interactions among circ_0081069, miR‐195‐5p, and SPIN1 were identified by dual‐luciferase reporter assay and RNA Immunoprecipitation assay. Xenograft mouse model assay was performed to determine the effect of circ_0007841 on radiosensitivity in vivo. Circ_0081069 and SPIN1 expression were upregulated, whereas miR‐195‐5p was downregulated in ESCC tissues, ESCC cells, and radiation‐stimulated ESCC cells. Circ_0081069 silencing inhibited ESCC cell proliferation, invasion, and migration but improved cell apoptosis. In addition, circ_0081069 knockdown enhanced ESCC cell radiosensitivity in vitro and in vivo. Circ_0081069 bound to miR‐195‐5p and regulated radiosensitivity by binding to miR‐195‐5p in ESCC cells. Moreover, SPIN1, a target of miR‐195‐5p, rescued miR‐195‐5p‐mediated effects in ESCC cells. Circ_0081069 was secreted from ESCC cells by being packaged into exosomes. Further, circ_0081069‐Exo inhibited radiosensitivity in ESCC cells. Exosome‐mediated transfer of circ_0081069 induced SPIN1 production by binding to miR‐195‐5p, further inhibiting radiosensitivity in ESCC.