circ_0041732 Promotes Breast Cancer Progression

Abstract

Breast cancer (BC) is a quite prevalent cancer worldwide, and it is the leading cause of cancer-related deaths among female population worldwide. Increasingly more efforts have been made in exploration of circular RNA (circRNA) functions in various malignancies. In this study, the primary target was to verify the putative influences of circ_0041732 on BC 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 up-regulation of circ_0041732 was confirmed in BC tissues and cell lines. E2F4 was proved to transcriptionally modulate circ_0041732. Moreover, circ_0041732 was validated to accelerate BC cell proliferation and impede G2/M arrest and cell apoptosis, and the oncogenic role of circ_0041732 in BC was further verified via in vivo experiments. Circ_0041732 could sponge miR-541-3p to enhance expression levels of RelA and GLI4, thus activating NF-kB and Hedgehog pathways and affecting BC cell proliferation, cell cycle and apoptosis. In all, E2F4-mediated circ_0041732 could activate RelA/NF-kB and GLI4/Hedgehog signaling pathways via modulation on miR-541-3p/RelA/GLI4 to promote BC progression.

The crosstalk between non-coding RNAs and cell-cycle events: A new frontier in cancer therapy

“… 151 Likewise, aberrant upregulation of circ_0041732 has been observed in breast cancer tissues and cell lines. 152 E2F4, which is frequently overactivated in breast cancer, acts as a transcription factor of circ_0041732. 153 Circ_0041732 binds to miR-541 and acts as a sponge to inhibit miR-541-induced silencing of CDC2 and cyclin B1, thereby affecting the cell cycle in breast cancer.…”

“…The silencing of circ_0041732 decreases CDC2 and cyclin B1 expression, inducing G2/M arrest and apoptosis in cancer cells. 152 Similarly, circRNA circ_0136666 regulates CDK6 expression by acting as a ceRNA of its targeting miRNA miR-1299. Circ_0136666 overexpression downregulates miR-1299, upregulating its target CDK6, and increases cell proliferation.…”