Hsa_circ_0021727 (circ-CD44) promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway

Abstract Background: The morbidity and mortality of esophageal squamous cell carcinoma (ESCC) remain high globally. Circular RNAs (circRNAs) play an important role in tumor progression. We discovered a novel aberrantly expressed circRNA (hsa_circ_0021727) in ESCC patients. However, the mechanism of hsa_circ_0021727 in tumors is still not elucidated. The purpose of this article is to investigate the biological role of hsa_circ_0021727 and its role in ESCC progression. Methods: Microarray analysis was used to screen diferentially expressed novel circRNAs.qRT-PCR,RNA-ISH and FISH were used to analyze the expression and localization of hsa_circ_0021727.MTT, colony formation, EdU, transwell assay, three-dimensional (3D) spheroid invasion assays and wound healing assays were used to describe biological effects on ESCC cells.Xenograft experiment and tail vein injection experiment were used to analyze tumor growth and metastasis in vivo.RNA-sequencing was used to identify hsa_circ_0021727 downstream targets.Western blot was used to detect the downstream protein expression of hsa_circ_0021727.RNA pulldown and dual luciferase experiments were used to evaluate the interaction of hsa_circ_0021727, miR-23b-5p and TAB1. Results: We screened a novel circRNA (hsa_circ_0021727) whose expression was upregulated in ESCC patients.ESCC patients with high expression of hsa_circ_0021727 had shorter survival time.Hsa_circ_0021727 promoted the proliferation, invasion and migration of ESCC cells. However, miR-23b-5p inhibited this ability of hsa_circ_0021727. MiR-23b-5p acts by targeting TAB1. In conclusion, hsa_circ_0021727 promoted ESCC progression by upregulating the expression of TAK1-binding protein 1(TAB1) via "sponge adsorption" of miR-23b-5p. In addition, in vivo experiments also confirmed that hsa_circ_0021727 can promote the proliferation, invasion and migration of ESCC cells. Conclusions： Hsa_circ_0021727 (circ_CD44) promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway.These findings may provide potential targets for the treatment of ESCC.