Blocking circ_0000520 Suppressed Breast Cancer Cell Growth, Migration and Invasion Partially via miR-1296/SP1 Axis...

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.

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.

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.

circ_0000520 knockdown could suppress cell growth, migration and invasion both in vitro and in vivo through regulating miR-1296/SP1 pathway.