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Circ_0001777 affects Triple-negative breast cancer progression through the miR-95-3p/AKAP12 axis

Published:November 19, 2022DOI:https://doi.org/10.1016/j.clbc.2022.11.004

      Abstract

      Background

      Triple Negative Breast Cancer (TNBC) is one of the most serious cancer. Circular RNA_0001777 (circ_0001777) expression was decreased in TNBC tissues. However, the molecular mechanism of circ_0001777 remains unknown.

      Methods

      The expression of circ_0001777, microRNA-95-3p (miR-95-3p) and A-kinase anchor protein 12 (AKAP12) were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). A series of in vitro experiments were designed to explore the function of circ_0001777 in TNBC cells and the regulatory mechanism between circ_0001777 and miR-95-3p and AKAP12 in TNBC cells. Western blot examined the relative protein levels in TNBC cells. Bioinformatics prediction site predicted the relationship between miR-95-3p and circ_0001777 or AKAP12 and was verified by Dual-luciferase reporter assays. The xenotransplantation model was established to study the role of circ_0001777 in vivo.

      Results

      The expression of circ_0001777 and AKAP12 was decreased in TNBC tissues, while the expression of miR-95-3p was increased. Circ_0001777 can sponge miR-95-3p, and AKAP12 is the target of miR-95-3p. In vitro complement experiments, overexpression of circ_0001777 significantly decreased the malignant behavior of TNBC, while co-transfection of miR-95-3p partially up-regulated this change. In addition, AKAP12 knockdown increased the proliferation, migration, and invasion of TNBC cells inhibited by overexpression of circ_0001777. Mechanically, circ_0001777 regulates AKAP12 expression in TNBC cells by sponge miR-95-3p. In addition, in vivo studies have shown that overexpression of circ_0001777 inhibits tumor growth.

      Conclusion

      Overexpression of circ_0001777 decreased proliferation, migration, and invasion of TNBC cells by regulating the miR-95-3p/AKAP12 axis, suggesting that circ_0001777/miR-95-3p/AKAP12 axis may be a potential regulatory mechanism for the treatment of TNBC
      Micro Abstract: We found that circ_0001777 positively regulates AKAP12 through sponge miR-95-3p, thereby inhibiting TNBC progression. These findings provide new targets for follow-up research and treatment of TNBC.

      Keywords

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