Hsa_circ_0002496 promotes the growth, angiogenesis, and stemness of breast cancer cells via miR‐433‐3p/YWHAZ cascade

Abstract

AbstractBackgroundBreast cancer (BC) has been studied more and more in modern medicine. Circ_0002496 has established a critical role in BC. MiR‐433‐3p can exert important activity in cancer. YWHAZ can participate in BC development, but the targeting relationship among the three variables and its influence on the related process of BC are not clear.MethodsRT‐qPCR was used to analyze circ_0002496, miR‐433‐3p, and YWHAZ expression. Immunoblotting was used to analyze YWHAZ, Bax, Bcl‐2, and PI3K/AKT‐related proteins. RNase R assay was used to verify the ring structure of circ_0002496. Cell phenotypes were tested by Cell Counting Kit 8, EdU, sphere formation, tube formation, and flow cytometry assays.ResultsCirc_0002496 was enhanced and MiR‐433‐3p was downregulated in BC, while the expression of YWHAZ was higher in BC. Circ_0002496 targeted miR‐433‐3p and miR‐433‐3p targeted YWHAZ in BC cells. Depletion of circ_0002496 influenced the BC process, but miR‐433‐3p inhibitor reversed the impact of si‐circ_0002496 on the BC process. Re‐expression of YWHAZ weakened the influence of miR‐433‐3p on the BC process. Depletion of circ_0002496 could astrict tumor growth in vivo. Moreover, the circ_0002496/miR‐433‐3p/YWHAZ axis mediated the activation of the PI3K/AKT signaling pathway.ConclusionCirc_0002496 participated in the malignant procession of BC by miR‐433‐3p/YWHAZ regulation cascade.