Circular RNAs (circRNAs) are recently discovered as a special novel type of endogenous noncoding RNAs (ncRNAs), which form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. Recent research revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, as well as interact with RNA-binding proteins (RBPs). In this review, not only the function and mechanism, but also the experimental methods of circRNA are summarized. The summary of the current state of circRNA will help us in the discovery of novel biomarkers, the therapeutic targets and their potential significance in diagnosis and treatment of diseases. CircRNAs might play important roles in cancers especially in hepatocellular carcinoma, gastric carcinoma and colorectal cancer as well as serving as diagnostic or predictive biomarkers of some diseases and providing new treatments of diseases.

Background: As new biomarkers of coronary artery diseases (CAD) emerge via metabolomics, the underlying functional mechanisms remain to be elucidated. Functional metabolomics aims to translate metabolomics-derived biomarkers to disease mechanisms. Methods: A cohort of 2324 patients who underwent coronary angiography from 4 independent centers was studied. A combination of ultra–performance liquid chromatography and quadrupole time-of-flight mass spectrometry in the negative ion mode was used for untargeted analysis of metabolites in plasma. Significant differential metabolites were identified by cross-comparisons with and within CAD types, including normal coronary artery, nonobstructvie coronary atherosclerosis, stable angina, unstable angina, and acute myocardial infarction. A tandem liquid chromatography-mass spectrometry–based approach using isotope-labeled standard addition was subsequently performed for targeted analysis of the metabolic marker N -acetylneuraminic acid (Neu5Ac). A functional metabolomics strategy was proposed to investigate the role of Neu5Ac in the progression of CAD by using in vitro and in vivo models. Results: We identified a total of 36 differential metabolites, 35 of which were confirmed with reference compounds. Elevation of Neu5Ac was observed in plasma during CAD progression in center 1 ( P =4.0e-64, n=2019) and replicated in 3 independent centers (n=305). The increased level of Neu5Ac in plasma was confirmed by accurate targeted quantification. Mechanistically, Neu5Ac was able to trigger myocardial injury in vitro and in vivo by activation of the Rho/Rho-associated coiled-coil containing protein kinase signaling pathway through binding to RhoA and Cdc42, but not Rac1. Silencing neuraminidase-1, the enzyme that regulates Neu5Ac generation, ameliorated oxygen-glucose deprivation–induced injury in cardiomyocytes and ligation/isoprenaline-induced myocardial ischemia injury in rats. Pharmacological inhibition of neuraminidase by anti-influenza drugs, oseltamivir and zanamivir, also protected cardiomyocytes and the heart from myocardial injury. Conclusions: Functional metabolomics identified a key role for Neu5Ac in acute myocardial infarction, and targeting neuraminidase-1 may represent an unrecognized therapeutic intervention for CAD.

A six-microRNA panel in plasma was identified as a potential biomarker for lung adenocarcinoma diagnosis

Cancer-secreted exosomes are critical mediators of cancer-host crosstalk. In the present study, we showed the delivery of miR-21-5p from colorectal cancer (CRC) cells to endothelial cells via exosomes increased the amount of miR-21-5p in recipient cells. MiR-21-5p suppressed Krev interaction trapped protein 1 (KRIT1) in recipient HUVECs and subsequently activated β-catenin signaling pathway and increased their downstream targets VEGFa and Ccnd1, which consequently promoted angiogenesis and vascular permeability in CRC. A strong inverse correlation between miR-21-5p and KRIT1 expression levels was observed in CRC-adjacent vessels. Furthermore, miR-21-5p expression in circulating exosomes was markedly higher in CRC patients than in healthy donors. Thus, our data suggest that exosomal miR-21-5p is involved in angiogenesis and vascular permeability in CRC and may be used as a potential new therapeutic target.

Background: Circulating miRNAs in serum may serve as promising diagnostic biomarkers for patients with gastric cancer. Methods: Using qRT-PCR-based Exiqon panel, we identified 58 differentially expressed miRNAs from three gastric cancer pool samples and one normal control (NC) pool in the initial screening phase. Identified miRNAs were further validated in the training (49 gastric cancer vs. 47 NCs) and validation phases (154 gastric cancer vs. 120 NCs) using qRT-PCR. The expression levels of the miRNAs were also determined in tissues, arterial serum, and exosomes. Results: Consequently, six serum miRNAs (miR10b-5p, miR132-3p, miR185-5p, miR195-5p, miR-20a3p, and miR296-5p) were significantly overexpressed in gastric cancer compared with NCs. The areas under the receiver operating characteristic curve of the six-miRNA panel were 0.764 and 0.702 for the training and validation phases, respectively. miR10b-5p and miR296-5p were significantly upregulated in gastric cancer tissues (n = 188). In addition, patients who did not receive adjuvant chemotherapy with high expression of miR10b-5p or miR296-5p in tissues tended to suffer worse overall survival. Furthermore, the expression levels of miR10b-5p, miR195-5p, miR20a-3p, and miR296-5p were significantly elevated in exosomes from gastric cancer serum samples (n = 30). Conclusions: We identified a six-miRNA panel in serum for the detection of gastric cancer. Impact: Our findings provide a novel serum miRNA signature for gastric cancer diagnosis, and will serve as the basis of the application of circulating miRNAs in clinical for the detection of gastric cancer in the future. Cancer Epidemiol Biomarkers Prev; 26(2); 188–96. ©2016 AACR.