Circular RNAs (
circRNAs) play important roles in
carcinogenesis. Here, we investigated the mechanisms and clinical significance of circ-NOL10, a highly repressed
circRNA in
breast cancer. Subsequently, we also identified
RNA-binding proteins (RBPs) that regulate circ-NOL10. Bioinformatics analysis was utilized to predict regulatory RBPs as well as circ-NOL10 downstream
microRNAs (
miRNAs) and
mRNA targets.
RNA immunoprecipitation,
luciferase assay, fluorescence in situ hybridization, cell proliferation, wound healing,
Matrigel invasion, cell apoptosis assays, and a xenograft model were used to investigate the function and mechanisms of circ-NOL10 in vitro and in vivo. The clinical value of circ-NOL10 was evaluated in a large cohort of
breast cancer by quantitative real-time PCR. Circ-NOL10 is downregulated in
breast cancer and associated with aggressive characteristics and shorter survival time. Upregulation of circ-NOL10 promotes apoptosis, decreases proliferation, and inhibits invasion and migration. Furthermore, circ-NOL10 binds multiple
miRNAs to alleviate
carcinogenesis by regulating PDCD4. CASC3 and metadherin (MTDH) can bind directly to circ-NOL10 with characterized motifs. Accordingly, ectopic expression or depletion of CASC3 or MTDH leads to circ-NOL10 expression changes, suggesting that these two RBPs modulate circ-NOL10 in
cancer cells. circ-NOL10 is a novel
biomarker for diagnosis and prognosis in
breast cancer. These results highlight the importance of therapeutic targeting of the RBP-
noncoding RNA (ncRNA) regulation network.