Identification of a novel circ_0001946/miR‐1290/SOX6 ceRNA network in esophageal squamous cell cancer

Abstract Background Circular RNAs (circRNAs) can function as competing endogenous RNAs (ceRNAs) to impact the development of esophageal squamous cell cancer (ESCC). Human circ_0001946 has been identified as a potential anticancer factor in ESCC, yet our understanding of its molecular basis remains limited. Methods Circ_0001946, microRNA (miR)‐1290 and SRY‐box transcription factor 6 (SOX6) were quantified by quantitative reasl‐time PCR (qRT‐PCR) or immunoblotting. Cell proliferation was assessed by CCK‐8 and EDU assays. Cell apoptosis and invasion were evaluated by flow cytometry and transwell assays, respectively. Cell migration was detected by transwell and wound‐healing assays. The direct relationship between miR‐1290 and circ_0001946 or SOX6 was determined by dual‐luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model assays were used to assess the role of circ_0001946 in tumor growth. Results Circ_0001946 expression was attenuated in human ESCC, and circ_0001946 increase impeded cell proliferation, invasion, migration and enhanced apoptosis in vitro. Moreover, circ_0001946 increase diminished xenograft growth in vivo. Mechanistically, circ_0001946 bound to miR‐1290, and re‐expression of miR‐1290 reversed circ_0001946‐dependent cell properties. SOX6 was a miR‐1290 target and it was responsible for the regulation of miR‐1290 in cell properties. Furthermore, circ_0001946 functioned as a ceRNA to regulate SOX6 expression via miR‐1290. Conclusion Our findings uncover an undescribed molecular mechanism, the circ_0001946/miR‐1290/SOX6 ceRNA crosstalk, for the anti‐ESCC activity of circ_0001946.