CircRNA circ_0023984 promotes the progression of esophageal squamous cell carcinoma via regulating miR-134-5p/cystatin-s axis

Abstract

ABSTRACT Recent studies have shown that circRNAs can act as oncogenic factors or tumor suppressors by sponging microRNAs (miRNAs). The upregulation of circ_0023984 was reported in esophageal squamous cell carcinoma (ESCC). However, its functional role in ESCC remain unclear. In the present study, circ_0023984 expression in ESCC cells and tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). Subcellular fraction experiment was performed to determine relative nuclear-cytoplasmic localization. The loss-of-function effects of circ_0023984 in ESCC cell lines were investigated by shRNA-mediated knockdown. Functional assays including cell Counting Kit-8 (CCK-8), 5-Ethynyl-2’-deoxyuridine (EDU) incorporation, colony formation and Transwell migration assays were conducted to assess the malignant phenotype. The interaction between the two molecules was analyzed by RNA pull-down, luciferase reporter assay and RNA immunoprecipitation (RIP). The subcutaneous tumor model in nude mice was used to assess the role of circ-0023984 in tumorigenesis. We found that ESCC patients with high circ_0023984 expression was associated with a poor prognosis. The knockdown of circ_0023984 suppressed cell growth, invasion, and migration in ESCC cells. Circ_0023984 interacted with miR-134-5p and inhibited its activity, which promoted the expression of CST4 (Cystatin-S). Circ_0023984 also regulated tumorigenesis in a CST4-dependent manner. Together, our study indicates that the oncogenic role of Circ_0023984 is mediated by miR-134-5p/CST4 Axis in ESCC, which could serve as potential targets for future therapeutic strategies.