Circ_0006168 Promotes the Migration, Invasion and Proliferation of Esophageal Squamous Cell Carcinoma Cells via miR-516b-5p-Dependent Regulation of XBP1.

Background: Circular RNAs (circRNAs) exert important roles in carcinogenesis. Here, we aimed to uncover the working mechanism of circ_0006168 in esophageal squamous cell carcinoma (ESCC) development.

Methods: Western blot assay and real-time quantitative polymerase chain reaction (RT-qPCR) were used to determine protein and RNA expression, respectively. Wound healing assay and transwell migration assay were performed to assess cell migration ability, whereas cell invasion ability was evaluated by transwell invasion assay. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay were utilized to analyze cell proliferation ability. Xenograft tumor model was utilized to assess the role of X-box binding protein 1 (XBP1) in xenograft tumor growth in vivo. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were used to verify intermolecular interactions.

Results: XBP1 silencing suppressed the migration, invasion and proliferation of ESCC cells in vitro and restrained the xenograft tumor growth in vivo. MicroRNA-516b-5p (miR-516b-5p) interacted with the 3' untranslated region (3'UTR) of XBP1 in ESCC cells. MiR-516b-5p overexpression inhibited the proliferation and motility of ESCC cells. MiR-516b-5p was a molecular target of circ_0006168 in ESCC cells. The interference of circ_0006168 restrained the motility and proliferation of ESCC cells. Circ_0006168 acted as miR-516b-5p sponge to up-regulate XBP1 expression in ESCC cells. MiR-516b-5p silencing or the accumulation of XBP1 largely rescued the proliferation ability and motility in circ_0006168-silenced ESCC cells.

Conclusion: In conclusion, circ_0006168 contributed to ESCC development through promoting the proliferation and motility of ESCC cells via mediating miR-516b-5p/XBP1 axis.