Abstract

Circular RNAs (circRNAs) have been demonstrated to play critical roles in the initiation and development of breast cancer (BC). This study aimed to uncover the regulatory roles of a novel circRNA, circRPPH1 (hsa_circ_0000514) in BC progression. CircRPPH1, miR-296-5p and FOXP4 levels were determined by qRT-PCR. CircRPPH1 stability was detected in response to ribonuclease (RNase) R digestion and actinomycin D treatment. Cell growth, migration and invasion were evaluated using various functional experiments. Protein levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), hexokinase 2 (HK2) and forkhead box protein 4 (FOXP4) were measured by Western blotting. Metabolic alterations of BC cells were evaluated using commercial kits. The interaction between miR-296-5p and circRPPH1/FOXP4 was assessed using dual-luciferase assay, RNA pull-down, and RNA immunoprecipitation (RIP) assay. The in vivo tumorigenesis was assessed in nude mice. According to the results, up-regulation of circRPPH1 was closely correlated with the poor prognosis of BC patients. Functional experiments showed that knockdown of circRPPH1 repressed BC cell growth, migration, invasion, glycolysis, and in vivo tumor growth. In addition, circRPPH1 could sponge miR-296-5p to enhance FOXP4 expression in BC cells. miR-296-5p inhibition or FOXP4 overexpression restored the malignant properties of circRPPH1-silenced BC cells. Thus, circRPPH1 promoted BC malignant progression through regulating miR-296-5p/FOXP4 axis, indicating a possible novel therapeutic strategy involving circRNA for BC patients.