circ-NOL10 regulated by MTDH/CASC3 inhibits breast cancer progression and metastasis via multiple miRNAs and PDCD4.

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