Cell-free circular RNAs (circRNAs) stably and abundantly exist in body fluids. In this study we aimed to investigate the potential of urinary cell-free circRNAs as a novel class of non-invasive disease biomarkers for diagnosis of bladder cancer. Differentially expressed circRNAs from 10 normal and 10 bladder cancer urine samples were firstly detected by microarray. Hsa_circ_0137439 was then screened and validated in 30 normal and 116 bladder cancer samples. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_0137439. The Kaplan-Meier method was used to evaluate the significance of hsa_circ_0137439 in the prognosis of bladder cancer. We found that hsa_circ_0137439 was significantly upregulated in bladder cancer samples. Moreover, increased expression of hsa_circ_0137439 was correlated with higher tumor stage, higher tumor grade, higher lymph node status, and history of muscle-invasive bladder cancer (MIBC). Also, urinary cell-free hsa_circ_0137439 could not only differentiate bladder cancer from normal controls but also distinguish MIBC from non-muscle-invasive bladder cancer (NMIBC). Additionally, hsa_circ_0137439 in urine supernatant could serve as an independent prognostic predicator of recurrence-free survival and overall survival for patients with bladder cancer. Cell assays showed that hsa_circ_0137439 knockdown contributed to the inhibition of cell proliferation and migration via hsa_circ_0137439/miR-142-5p/MTDH axis. In conclusion, urinary cell-free hsa_circ_0137439 could be a promising biomarker for tumor diagnosis and prognostic assessment of bladder cancer patients.

No detectable neurodevelopment deficit was observed in offspring up to 24 months old from mothers who had gestational SCH.