Withdrawal: Circ_0008078 Inhibits EC Cell Tumour Properties by Mir‐191‐5p‐dependent Regulation of ELOVL4

Background Esophagus cancer (EC) is an aggressive malignant cancer in the world, and its progression involves the regulation of circular RNA (circRNA). This study is designed to reveal the role of circ_0008078 in EC development and the underlying mechanism. Methods RNA expression of circ_0008078, miR-191-5p, ELOVL fatty acid elongase 4 (ELOVL4), cyclin D1, and proliferating cell nuclear antigen (PCNA) was detected by qRT-PCR or Western blotting. Nuclear proliferation marker (Ki67) expression was analyzed by immunohistochemistry (IHC) assay. The overall survival rate of EC patients was assessed by Kaplan-Meier method. Cell proliferation, apoptosis, angiogenesis ability, migration, and invasion were investigated by 5-Ethynyl-2’-deoxyuridine (EdU) assay, flow cytometry analysis, tube formation assay, wound-healing assay, and transwell invasion assay, respectively. The associations among circ_0008078, miR-191-5p, and ELOVL4 were identified by dual-luciferase reporter assay. Results Circ_0008078 expression was downregulated in EC tissues (N=35) and cells compared with normal esophageal tissues (N=35) and cells (P<0.0001). Low circ_0008078 expression predicted a poor prognosis for EC patients (P=0.0068). The increased expression of circ_0008078 led to inhibition on cell proliferation, tube formation, migration and invasion but promotion on cell apoptosis (P<0.0001). Re-expression of miR-191-5p, a target miRNA of circ_0008078, attenuated circ_0008078 overexpression-induced effects in EC cells (P<0.0001). In addition, miR-191-5p combined with ELOVL4 to regulate EC cell tumor properties. Circ_0008078 induced ELOVL4 expression by negatively modulating miR-191-5p (P<0.0001). Further, ectopic expression of circ_0008078 inhibited EC cell malignancy in vivo (P<0.001). Conclusion Circ_0008078 inhibited EC cell malignancy by the miR-191-5p/ELOVL4 pathway, providing a possible target for EC therapy.