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

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.