Circ-UBR1 facilitates proliferation, metastasis, and inhibits apoptosis in breast cancer by regulating the miR-1299/CCND1 axis

Aims:Circular RNA (circRNA) is abnormally expressed in cancers and has been linked to cancer progression, including breast cancer (BC). However, the role and mechanism of circ-UBR1 in BC progression remains to be further studied.

Materials and methods:Quantitative real-time PCR (qRT-PCR) was conducted to analyze the expression of circ-UBR1, miR-1299 and Cyclin D1 (CCND1). Cell counting kit 8 (CCK8) assay was used to measure cell viability. Cell apoptosis and cell cycle distribution were analyzed by flow cytometry. Then, the migration and invasion of cells were determined by transwell assay. Moreover, BC tumor xenograft model was built to evaluate the function of circ-UBR1 silencing on BC tumor volume and weight. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to illuminate the interaction between miR-1299 and circ-UBR1 or CCND1. In addition, relative CCND1 protein expression was assessed using western blot (WB) analysis.

Key findings:Our results revealed that circ-UBR1 was upregulated in BC, and its silencing could inhibit BC cell proliferation, metastasis, and promote apoptosis in vitro, as well as restrain BC tumor growth in vivo. Meanwhile, we found that circ-UBR1 could sponge miR-1299, and miR-1299 inhibitor could reverse the effect of circ-UBR1 knockdown on BC cell progression. Furthermore, CCND1 was a target of miR-1299, and CCND1 overexpression could reverse the effect of miR-1299 mimic on BC cell progression. Also, the downregulation of circ-UBR1 could inhibit CCND1 expression, while this effect could be inverted by miR-1299 inhibitor.

Significance:Our data indicated that circ-UBR1 might play a pro-cancer role in BC progression by regulating the miR-1299/CCND1 axis.

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