The circRNA circKNSTRN promotes breast cancer progression by modulating the miR-320a-3p/SPAG5 axis.

Breast cancer (BC) ranks as the most prevalent cancer and the primary cause of cancer-related mortality among women globally. Our previous research has proved that Sperm-associated antigen 5 (SPAG5) is a potential prognostic biomarker in BC. However, the possible biological function and molecular mechanism of SPAG5 in BC remain unknown. Next, we identified a circular RNA, circKNSTRN (hsa_circ_0103433), upstream of SPAG5, which may synergize with SPAG5 to impact BC. In this study, we aimed to explore the association between circKNSTRN and SPAG5 and their roles, especially the function of circKNSTRN in BC. The existence of circKNSTRN was confirmed by the Sanger sequence and RT-PCR. High expression level of circKNSTRN was tested in human BC cell lines and tissues by RT-qPCR. Functionally, the overexpression of circKNSTRN facilitated the proliferation and migration of BC cells, while also regulating cell apoptosis and cell cycle. Conversely, the knockdown of circKNSTRN yielded the opposite results. Mechanistically, miR-320a-3p was shown to bind to circKNSTRN and inhibit the proliferation and migration abilities of BC cells through bioinformatic analysis, dual-luciferase reporter assays, RNA pull-down experiments, and FISH assays. The inhibition of miR-320a-3p reverses the effect. Moreover, circKNSTRN regulated the expression level of SPAG5 by sponging miR-320a-3p. Significance: circKNSTRN was first identified and proved to promote the progression of BC through the miR-320a-3p/SPAG5 axis. The circKNSTRN/miR-320a-3p/SPAG5 axis may serve as a promising therapeutic and prognostic target for BC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-29343-1.