Background: Breast cancer (BCa) is an overwhelming malignant tumor mainly in women globally. Circular RNAs (circRNAs) are a special type of noncoding RNAs involved in competing endogenous RNA (ceRNA) network, a classic molecular mechanism of the tumorigenesis of human cancers, including BCa. Here, we intended to explore the role and mechanism of hsa_circ_0000520  (circ_0000520 ) in BCa cells.
Methods: Expression of circ_0000520 , miRNA-1296-5p  (miR-1296 ) and specificity protein 1  (SP1 ) was measured by real time-quantitative PCR and Western blotting. Cell growth was measured by cell counting kit-8, colony formation assay and flow cytometry method. Cell migration and invasion were assessed by transwell assays and Western blotting. Tumor growth was determined by xenograft models. The direct interaction among circ_0000520 , miR-1296  and SP1  was confirmed by dual-luciferase reporter assay and RNA pull-down assay.
Results: circ_0000520  was upregulated in BCa tumors and cell lines (T47D, MCF7, MDA-MB-231, BT549, and SKBR3), and circ_0000520  high expression was associated with poor overall survival. Blocking circ_0000520  suppressed cell viability, colony formation, migration and invasion, but promoted cell cycle arrest and apoptosis rate in MDA-MB-231 and MCF7 cells. circ_0000520  could directly regulate miR-1296  expression, and SP1  was a novel target for miR-1296 . Moreover, the anti-tumor role of circ_0000520  silencing was abrogated by miR-1296  downregulation or SP1  restoration. Notably, tumor growth of MDA-MB-231 cells in mice was restrained by circ_0000520  deletion.
Conclusion: circ_0000520  knockdown could suppress cell growth, migration and invasion both in vitro and in vivo through regulating miR-1296/SP1  pathway.
Keywords: circ_0000520 , breast cancer, BCa, miR-1296 , SP1