Abstract
Exosomal miRNAs (EmiRs) can be used for prediction of gastric cancer (GC) development. Supposedly, both plasma and urinary microRNAs can also be potential biomarkers for screening, but the diagnostic values of EmiRs in blood and urine are not fully studied. We here collected both types of samples from GC patients and healthy individuals and conducted miRNA sequencing to identify key members of EmiRs in GC. The exosomes samples derived from blood and urine were collected from 3 healthy individuals and 7 GC patients. Differentially expressed miRNAs (DEmiRNAs) were acquired, ontology enrichment analysis and Protein-protein Interaction (PPI) enrichment analysis were performed. There were 8 DEmiRNAs in the serum and 3 DEmiRNAs in the urine. For GC patients, there were three up-regulated DEmiRNAs (hsa-miR-130b-3p, hsa-miR-151a-3p and hsa-miR-15b-3p) in the serum exosomes, and one up-regulated DEmiRNA (hsa-miR-1246) in the urinary exosomes. Using miRNA target prediction databases, we found 418 common targets of hsa-miR-15b-3p, 35 common targets of hsa-miR-151a-3p, 117 common targets of hsa-miR-130b-3p, and 357 common targets of hsa-miR-1246. Some commonly enriched ontology terms were found, including GO BP terms like cell surface receptor signaling pathway involved in cell-cell signaling, positive regulation of catabolic process, morphogenesis of an epithelium, and GO CC terms perinuclear region of cytoplasm. The PPI network show some key nodes, including TAOK1, CMTM6, SCN3A, WASF3, IGF1, CNOT7, GABRG1, PRKD1. Together, this study provided an integrative analysis of expression profile of key circulating exosomal microRNAs. Four key exosomal miRNAs (hsa-miR-130b-3p, hsa-miR-151a-3p and hsa-miR-15b-3p) and the interaction network or enrichments based on their targets (TAOK1, CMTM6, SCN3A, WASF3, IGF1, CNOT7, GABRG1, PRKD1) may provide a reference of the molecular mechanisms in the GC development.
Highlights
Gastric cancer (GC) is the fourth most common malignance worldwide [1]
Previous studies observed the samples of plasma exosomal miRNAs (EmiRs) for prediction of GC development, progression, and treatment outcomes
For GC patients, there were 3 up-regulated DEmiRNAs in the serum exosomes, and one DEmiRNA enriched in the urinary exosomes. These up-regulated miRNAs may be transferred to tissues or cells and target specific RNAs, which promotes the GC development
Summary
Gastric cancer (GC) is the fourth most common malignance worldwide [1]. An exact detection based on GC biomarkers has a high clinical significance. For GC patients, the exosomal microRNA (miRNA or miR) may have potential clinical application value in diagnosis and status evaluation [2, 3]. MicroRNA is a short-chain noncoding RNA molecule (around 22 nucleotides in length). It regulates protein expression of a particular mRNA (by incomplete base pairing), causing inhibition of protein translation of its target genes. Tumor secreted exosomes are sharply different among cancers, and between healthy individuals vs cancer patients. The diagnostic value of EmiRs in urine for GC is unknown, and that of plasma EmiRs is not fully studied We here collected both plasma samples and urine samples from GC patients and healthy control individuals for miRNA sequencing, and some key members were identified
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