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.