Breast cancer is quite a prevalent cancer worldwide, and it is the leading cause of cancer-related deaths among female populations worldwide. Increasingly more efforts have been made in exploration of circular RNA functions in various malignancies. In this study, the primary target was to verify the putative influences of circ_0041732 on breast cancer progression and the corresponding regulatory mechanism. In addition to measurement of RNAs and proteins, functional assays were done to examine the changes in cell proliferation and cell cycle, and the potential association among genes was investigated by mechanism assays. According to experimental results, significant upregulation of circ_0041732 was confirmed in breast cancer tissues and cell lines. E2F4 was proved to transcriptionally modulate circ_0041732. Moreover, circ_0041732 was validated to accelerate breast cancer cell proliferation and impede G2–M arrest and cell apoptosis, and the oncogenic role of circ_0041732 in breast cancer was further verified via in vivo experiments. circ_0041732 could sponge miR-541-3p to enhance expression levels of RelA and GLI4, thus activating NFκB and Hedgehog pathways and affecting breast cancer cell proliferation, cell cycle, and apoptosis. In all, E2F4-mediated circ_0041732 could activate RelA/NFκB and GLI4/Hedgehog signaling pathways via modulation on miR-541-3p/RelA/GLI4 to promote breast cancer progression.

Implications:

E2F4-mediated circ_0041732 upregulation resulted in the activation of NFκB and Hedgehog pathways via sponging miR-541-3p and enhancing expression levels of RelA and GLI4, thus affecting breast cancer cell proliferation, cell cycle, and cell apoptosis.

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