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EIF4A3-mediated hsa_circ_0088088 promotes the carcinogenesis of breast cancer by sponging miR-135-5p
Journal of Biochemical and Molecular Toxicology  (IF3.642),  Pub Date : 2021-08-30, DOI: 10.1002/jbt.22909
Qun Liu, Huiting Dong

Circular RNAs have participated in oncology progress. Nevertheless, the potential mechanisms are not completely understood. We intended to inspect the functions of hsa_circ_0088088 on breast malignancy, together with the possible mechanism(s). hsa_circ_0088088 expression in breast malignancy was studied using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The overall survival was studied by the Kaplan–Meier curve. The biological functions of hsa_circ_0088088 aberrant expression on cell growth and metastasis were evaluated in MDA-MB-231 cells. Bioinformatics analysis, RNA immunoprecipitation (RIP), and qRT-PCR were accomplished to confirm the possible regulatory effects of eukaryotic initiation factor 4A3 (EIF4A3) on the biogenesis of hsa_circ_0088088. Furthermore, a dual-luciferase reporter assay, qRT-PCR, and RNA pull-down assay were used to confirm the association between the hsa_circ_0088088 and miR-135-5p in MDA-MB-231 cells. hsa_circ_0088088 was upregulated in the tumor tissues and cells, and higher expression presented an unfavorable prognosis. hsa_circ_0088088 overexpression promoted cell growth and metastasis in MDA-MB-231 cells. EIF4A3 was found to positively regulate hsa_circ_0088088. Furthermore, we confirmed that hsa_circ_0088088 sponges miR-135-5p and directly targets miR-135-5p with respect to the cell growth and metastasis in MDA-MB-231 cells. Our data suggest that EIF4A3-induced hsa_circ_0088088 stimulates the carcinogenic effects of breast tumors by sponging miR-135-5p.