Circular RNA expression profiles in extracellular vesicles from the plasma of patients with pancreatic ductal adenocarcinoma

Abstract

Tumor‐derived extracellular vesicles (EVs) and their contents are involved in the development of human malignancies. Circular RNAs (circRNAs), enriched in EVs, can regulate diverse cellular processes by acting as microRNA (miRNA) sponges or through other mechanisms. In the present study, we explored the potential roles of circRNAs in EVs in the development of pancreatic ductal adenocarcinoma (PDAC). First, plasma was obtained from patients with PDAC (n = 8) and healthy volunteers (n = 8), and EVs were isolated by the ultracentrifugation method. Nanoparticle tracking analysis and transmission electron microscopy confirmed the size and form of the isolated EVs. The circRNA expression profiles of EVs were investigated by high‐throughput whole transcriptome sequencing. We then further validated the accuracy of the circRNA sequencing data by quantitative real‐time PCR analysis using plasma samples and PC cell lines, and subsequently performed bioinformatics analysis to reveal the potential functional roles of the differentially expressed circRNAs and to construct a circRNA‐miRNA interaction network to predict the target miRNAs of these circRNAs. Our work provides novel targets for further studies concerning the pathogenesis of PDAC.

Non-coding RNAs in Pancreatic Ductal Adenocarcinoma

“…Additional microarray data revealed that there were 115 upregulated and 141 downregulated circRNAs in PDACs (75). Another study uncovered that 453 circRNAs were differentially expressed and were significantly different in extracellular vesicles isolated from the plasma of 8 PDAC patients or healthy controls (76). It has been suggested that aberrant expression of circRNAs in PDAC are related to proliferation and development.…”

Practical guide for circular RNA analysis: Steps, tips, and resources

“…Beyond their localization in the nucleus and/or cytoplasm, are circRNAs distributed in other locales? Recent reports have identified circRNAs in extracellular vesicles, including those derived from tumor cells (Hon, Ab‐Mutalib, Abdullah, Jamal, & Abu, 2019; Lasda & Parker, 2016; Q. Li, Geng, et al, 2019; Y. Li, Zhao, et al, 2019; Shi et al, 2020). Are they only found in membrane‐enclosed structures or also in free solution?…”

Emerging Function and Clinical Significance of Exosomal circRNAs in Cancer

“…A total of 453 differentially expressed circRNAs, consisting of 274 upregulated and 179 downregulated circRNAs, were discovered in exosomes from the plasma of patients with pancreatic ductal adenocarcinoma (PDAC) relative to healthy volunteers. 159 It was proposed that these exosomal circRNAs might regulate PDAC pathogenesis by targeting miRNAs in recipient cells. Recently, 182 exosomal circRNAs were reported to be differentially expressed in the plasma from LUAD patients compared with healthy controls.…”