CircFBXL5 promotes the 5-FU resistance of breast cancer via modulating miR-216b/HMGA2 axis

Background: Circular RNAs (circRNAs) have been confirmed to be relevant to the 5-fluorouracil (5-FU) resistance of breast Cancer. Nevertheless, how and whether circRNA F-box and leucine-rich repeat protein 5 (circFBXL5) regulates the 5-FU resistance of breast Cancer is uncertain. This study aims to explore the function and mechanism of circFBXL5 in the 5-FU resistance of breast Cancer.

Methods: Thirty nine paired breast Cancer and normal tissues were harvested. circFBXL5, microRNA-216b (miR-216b) and high-mobility group AT-hook 2 (HMGA2) abundances were examined via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, 5-FU resistance, migration, invasion, and Apoptosis were tested via cell counting kit-8 assay, wound healing analysis, transwell analysis, and flow cytometry. The relationship of miR-216b and circFBXL5 or HMGA2 was tested via dual-luciferase reporter analysis and RNA pull-down assay. The impact of circFBXL5 on breast Cancer tumor growth in vivo was analyzed via xenograft model.

Results: circFBXL5 was highly expressed in breast Cancer tissues and cells, and was more upregulated in 5-FU-resistant breast Cancer cells. Function experiments showed that circFBXL5 knockdown inhibited the 5-FU resistance of breast Cancer by inhibiting cell migration, invasion and promoting Apoptosis. In the terms of mechanism, miR-216b could be sponged by circFBXL5, and its inhibitor could also reverse the influence of circFBXL5 silencing on the 5-FU resistance of breast Cancer cells. In addition, HMGA2 was a target of miR-216b, and its overexpression also reversed the regulation of miR-216b overexpression on the 5-FU resistance of breast Cancer. Furthermore, circFBXL5 interference declined breast Cancer tumor growth in xenograft model.

Conclusion: Our data showed that circFBXL5 could promote the 5-FU resistance of breast Cancer by regulating miR-216b/HMGA2 axis.