Circular RNA hsa_circ_0008039 promotes proliferation, migration and invasion of breast cancer cells through upregulating CBX4 via sponging miR-515-5p

摘要

OBJECTIVE: Breast cancer (BC) is the second most frequent malignancy worldwide. Hsa_circ_0008039 exerts the carcinogenic factors in BC. However, the pathogenesis of hsa_circ_0008039 involved in BC is still unclear. PATIENTS AND METHODS: The expression levels of hsa_circ_0008039, microRNA-515-5p (miR-515-5p) and chromobox homolog 4 (CBX4) in BC tissues and cells were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, migration and invasion were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) and transwell assays, severally. The binding relationship among hsa_circ_0008039, miR-515-5p and CBX4 was predicted by starBase, then verified by the dual-luciferase reporter assay and immunoprecipitation (RIP) assay. The interaction between hsa_circ_0008039 and miR-515-5p was confirmed by RNA pull-down assay. The protein level of CBX4 was detected by Western blot assay. The biological role of hsa_circ_0008039 was detected by xenograft tumor model in vivo. RESULTS: Hsa_circ_0008039 was upregulated in BC tissues and cells, and expedited proliferation, migration and invasion of BC cells. MiR-515-5p was downregulated in BC tissues and cells and worked as a target of hsa_circ_0008039. CBX4 was highly expressed in BC tissues and cells, and contributed to proliferation, migration and invasion of BC cells. Hsa_circ_0008039 enhanced CBX4 expression by competitively binding to miR-515-5p, thereby promoting BC development. Hsa_circ_0008039 knockdown repressed BC tumor growth in vivo. CONCLUSIONS: These findings implicated that hsa_circ_0008039 contributed to proliferation, migration and invasion in vitro and promoted tumor growth in vivo by miR-515-5p/CBX4 axis in BC, suggesting a potential therapeutic strategy for BC treatment.