Thoracic Cancer (Mar 2023)
Hsa_circ_0001925 promotes malignant progression in triple‐negative breast cancer via miR‐1299/YY1 axis
Abstract
Abstract Background Circular RNAs (circRNAs) are related to the pathogenesis and progression of triple‐negative breast cancer (TNBC). The aim of this study was to investigate the role and mechanism of hsa_circ_0001925 in TNBC progression. Methods Hsa_circ_0001925, microRNA (miR)‐1299 and Yin Yang 1 (YY1) levels were examined in TNBC via reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) and western blot. Cell counting kit‐8 (CCK‐8), colony formation, 5‐ethynyl‐2′‐deoxyuridine (EdU) staining, flow cytometry, wound healing assay and tube formation assay were conducted to estimate the effects of hsa_circ_0001925 on malignant phenotypes of TNBC tumors. Several protein levels were measured with western blot. The regulatory relationship between miR‐1299 and hsa_circ_0001925 or YY1 was validated using a dual‐luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft assay was used to estimate the effect of hsa_circ_0001925 in TNBC in vivo. Results Hsa_circ_0001925 and YY1 levels were upregulated, while miR‐1299 abundance was downregulated in TNBC tissues and cells. Hsa_circ_0001925 silencing constrained cell proliferation, migration and angiogenesis whereas it promoted apoptosis in vitro, and hsa_circ_0001925 silencing significantly curbed xenograft tumor growth in vivo. Hsa_circ_0001925 acted as a miRNA sponge for miR‐1299. Hsa_circ_0001925 decreased YY1 expression by sponging miR‐1299. MiR‐1299 downregulation alleviated the effects of hsa_circ_0001925 knockdown on BC progression. MiR‐1299 interacted with the 3′ untranslated region (3′ UTR) of YY1, and YY1 overexpression partly reversed the effects of miR‐1299 overexpression on BC progression. Conclusion Our findings showed that hsa_circ_0001925 mediated TNBC progression via regulating miR‐1299/YY1 axis, providing a potential target for BC treatment.
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