Exosomal hsa_circ_0008925 from Urine Is Related to Chronic Renal Fibrosis.

At present, there is no noninvasive biomarker of renal fibrosis. The potential diagnostic value of urinary exosome-derived circRNAs from glomerular disease patients for renal fibrosis is still uncertain. Here, we first detected the expression of hsa_circ_0008925 in TGF-ß1-cultured HK-2 cell-derived exosomes. Secondly, we collected urine samples from 95 biopsy-proven glomerular disease patients and 34 healthy controls. The expression of hsa_circ_0008925 was analyzed, and the correlation with renal function and pathological changes was calculated. The receiver operating characteristic (ROC) curve for the diagnosis of renal fibrosis was performed. The results showed that in exosomes derived from TGF-ß1-cultured HK-2 cells, the expression of hsa_circ_0008925 was increased compared with normal cultured. Further, the expression level of hsa_circ_0008925 was increased in urinary exosomes from renal fibrosis patients and correlated with serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate, and cystatin C. The level of hsa_circ_0008925 was furthermore correlated with the score of tubulointerstitial fibrosis (TIF) and the score of glomerular sclerosis. The ROC curve showed that hsa_circ_0008925 can diagnose renal fibrosis at a cut-off value of 0.093 with a sensitivity of 52.2% and specificity of 96.4%. In summary, we indicated that urinary exosomal hsa_circ_0008925 could be acted as a noninvasive biomarker for renal fibrosis in glomerular diseases patients.

Exploring Noninvasive Biomarkers with the miRandola Database: A Tool for Translational Medicine.

Noninvasive biomarkers are required for addressing crucial clinical needs. The ideal biomarker should be easily accessible and provide a unique characteristic for a healthy status or a pathological condition. In the last years, microRNAs (miRNAs) have been proposed as promising tissue-based biomarkers for several diseases such as cancer and cardiovascular diseases. Recently, miRNAs have shown great potential as novel noninvasive biomarkers, due to their high stability in human body fluids such as serum, plasma, and urine. Furthermore, many other noncoding RNAs (ncRNAs) such as long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have shown to be novel biomarkers as well. The aim of this exciting research field is to offer novel tools, allowing translational scientists to develop new strategies for diagnosis, screening, and monitoring of diseases. In this book chapter, the miRandola database and its applications will be introduced. The database offers the possibility to explore information on ncRNAs as noninvasive biomarkers, manually extracted from scientific literature and public available resources.

Underlying metastasis mechanism and clinical application of exosomal circular RNA in tumors (Review).

Circular RNA (circRNA) is a long non­coding RNA molecule with a closed loop structure lacking a 5'cap and 3'tail. circRNA is stable, difficult to cleave and resistant to RNA exonuclease or RNase R degradation. circRNA molecules have several clinical applications, especially in tumors. For instance, circRNA may be used for non­invasive diagnosis, therapy and prognosis. Exosomes play a crucial role in the development of tumors. Exosomal circRNA in particular has led to increased research interest into tumorigenesis and tumor progression. Additionally, exosomal circRNA plays a role in cell­cell communication. Exosomal circRNA facilitates tumor metastasis by altering the tumor microenvironment and the pre­metastatic niche. Additionally, studies have revealed the mechanism by which exosomal circRNA affects malignant progression through signal transduction. Moreover, exosomal circRNA promotes tumor metastasis by regulating gene expression, RNA transcription and protein translation. In this review, the biological features and clinical application of exosomal circRNA are described, highlighting the underlying mechanisms through which they regulate tumor metastasis. The application of circRNA as clinical diagnostic biomarkers and in the development of novel therapeutic strategies is also discussed.

The Research Progression and Clinical Significance of Circular RNAs in Head and Neck Cancers.

With rapid development of science technique and molecular research, a large number of circular RNAs (circRNAs) were discovered. CircRNAs that are a heterogeneous endogenous group of non-coding RNA not only are abundantly and diffusely expressed in mammals but also participate in many biological processes, such as in tumor ingenuity and progress. CircRNAs have rarely open reports in the head and neck cancers (HNC), which are an aggressive malignant tumor with unsatisfactory overall survival rates. The diagnostics and treatments continue to improve while the survival rate of HNC patients has no more obvious improvement. Recent studies that are aimed at exploring the molecular mechanisms of occurrence and progression of circRNAs in HNC provide a valuable insight into potential novel diagnostic and therapeutic approaches. In this review, we summarize the increasing number of published researches on the research progression of circRNAs in HNC, as well as their possible clinical implications on HNC.

Identification of urinary hsa_circ _0137439 as potential biomarker and tumor regulator of bladder cancer.

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 noninvasive 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.