Circ_0038632 Acts as a Sponge of miR-4306 to Facilitate Breast Cancer Progression Through Regulating CXCR4 Expression

Abstract

CircRNA plays an important role in the progression of breast cancer. This study focused on the molecular mechanism of circ_0038632 in regulating breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ_0038632, microRNA-4306 (miR-4306) and C-X-C chemokine receptor type 4 (CXCR4) mRNA in BC tissues and cells. Western blot was applied to detect the expression of CXCR4 protein and metastasis-related proteins (MMP2 and MMP9). Cell proliferation and apoptosis were observed by colony formation assay and flow cytometry. Scratch and Transwell assays were performed to detect the cell transfer ability. The angiogenesis ability of human vascular endothelial cells (HUVECs) was measured by the tube forming assay. Dual luciferase reporting assay was used to verify the relationship between miR-4306 and circ_0038632 or CXCR4. In vivo assay was used to detect the influence of circ_0038632 on the formation of BC tumors. Circ_0038632 and CXCR4 were highly expressed in BC tissue and cells, while miR-4306 was lowly expressed. Inhibition of circ_0038632 would restrain BC cell colony formation, migration, invasion, enhance cells apoptosis, and decrease HUVECs tube formation. Circ_0038632 acted as a sponge of miR-4306, and miR-4306 inhibitor would reverse the suppression effect of si-circ_0038632 in BC cells. CXCR4 was a target of miR-4306, and the overexpression of CXCR4 turned the growth inhibition of BC cells caused by exogenetic miR-4306. Importantly, circ_0038632 increased CXCR4 expression via sponging miR-4306. Finally, circ_0038632 knockdown inhibited the BC tumor formation. In conclusion, circ_0038632 contributed to the malignant progression of BC via regulating miR-4306/CXCR4 axis.