Circ-ATIC regulates esophageal squamous cell carcinoma growth and metastasis through miR-1294/PBX3 pathway

Esophageal squamous cell carcinoma (ESCC) is a digestive tract malignancy associated with poor clinical outcome. Growing evidence have elucidated that circular RNAs (circRNAs) play important roles in the pathological process of ESCC. However, the detailed mechanisms how circRNAs modulate the development of ESCC remain largely unknown. Our study aimed to decipher the role and mechanism of circ-ATIC (also termed as circRNA_0058063) in regulating the progression of ESCC. We found that circ-ATIC and its host gene ATIC were significantly increased in ESCC tissues and cells compared with the adjacent noncancerous tissues or normal esophagus epithelial cell. Circ-ATIC knockdown substantially reduced proliferation and the number of invaded ESCC cells and retarded EMT process, reflecting by the decreased N-cadherin and elevated E-cadherin. However, the level of host gene ATIC was not changed under circ-ATIC suppression. It was predicted that circ-ATIC could bind to miR-1294 and serve as a sponge RNA. The luciferase reporter assay and RNA immunoprecipitation (RIP) assay confirmed their relations. MiR-1294 was decreased in ESCC tissues and cells, which was reversely correlated with circ-ATIC level. Furthermore, PBX3 was predicted and proved to be a downstream direct target of miR-1294. PBX3 mRNA and protein were obviously upregulated in ESCC tumor tissues and cells. PBX3 overexpression could reverse the suppressive roles of miR-1294 mimics on ESCC proliferation and invasion. In an xenograft nude mice model, stable transfection of sh-circ-ATIC significantly retarded the growth of tumor and suppressed VEGF and Ki67. Collectively, circ-ATIC promoted ESCC proliferation and invasion by regulating miR-1294/PBX3 axis.