Circulating microRNAs and long non-coding RNAs in gastric cancer diagnosis

Gastric cancer (GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the most popular non-coding RNAs in cancer research. To date, the roles of miRNAs and lncRNAs have been extensively studied in GC, suggesting that miRNAs and lncRNAs represent a vital component of tumor biology. Furthermore, circulating miRNAs and lncRNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating miRNAs and lncRNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for miRNA secretion have been elucidated, including active secretion by microvesicles, exosomes, apoptotic bodies, high-density lipoproteins and protein complexes as well as passive leakage from cells. However, the mechanism underlying lncRNA secretion and the functions of circulating miRNAs and lncRNAs have not been fully illuminated. Concurrently, to standardize results of global investigations of circulating miRNAs and lncRNAs biomarker studies, several recommendations for pre-analytic considerations are put forward. In this review, the authors summarize the known circulating miRNAs and lncRNAs for GC diagnosis. The possible mechanism of miRNA and lncRNA secretion as well as methodologies for identification of circulating miRNAs and lncRNAs are also discussed.

Mechanisms of long non-coding RNA function. A: Serve as enhancer RNAs (eRNAs) to compete with nascent mRNA for negative elongation factor (NELF) complex binding at the target promoter for transcriptional regulation; B: Serve as a scaffolding base for the coordination of epigenetic or chromatin-modifying complexes; C: Serve as molecular sponges for microRNAs (miRNAs); D: Function as a decoy for miRNAs or translation factors to regulate gene expression; E: Hybridize with their corresponding spliced mRNAs to form dsRNAs, which are cleaved by Dicer to generate endogenous small interfering RNAs (endo-siRNAs) to modulate gene expression; F: Gene expression regulation by direct long non-coding RNA (lncRNA)-mRNA interactions; G: Directly modulate tumor suppressor signaling by either transcriptional regulation of tumor suppressor genes or mediation of tumor suppressor target gene activation.