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Exploration of differentially-expressed exosomal mRNAs, lncRNAs and circRNAs from serum samples of gallbladder cancer and xantho-granulomatous cholecystitis patients

ABSTRACT: Gallbladder cancer (GBC) is the most common biliary tract malignancy worldwide. Although a growing number of studies have been devoted to the mechanism’s exploration of GBC, few molecules can be utilized as a specific biomarker for GBC early diagnosis and therapeutic treatment. Recent studies have shown that exosomes not only participate in the progression of tumors, but also carry the specific information which can define multiple cancer types. The present study was carried out to investigate the expression profile of coding and non-coding RNAs (lncRNAs and circRNAs) in the plasma-derived exosomes from GBC patients. By using high-throughput RNA sequencing and subsequently bioinformatic analysis, we identified a number of differentially expressed (DE) mRNAs, lncRNAs and circRNAs in GBC-exosomes comparing to xantho-granulomatous cholecystitis (XGC)-exosomes. Then we applied Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analysis to investigate the potential function of these DE RNAs. Furthermore, we explored the interaction networks and competing endogenous RNA networks of these DE RNAs and their targeted genes, which revealed a complex regulatory network among coding and non-coding RNAs. In summary, this study will give evidence on the diagnostic worth of plasma-derived exosomes in GBC and provide a new perspective on the novel mechanism of GBC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE166915 | GEO | 2022/07/01

REPOSITORIES: GEO

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Project description:Purpose: This study aimed to explore the differential expression profiles of exosomal lncRNAs and evaluated their potential utility in the accurate diagnosis of LAA stroke. Methods: LncRNA profiles of exosomes in large artery atherosclerosis stroke and controls were generated by high-throughput sequencing. The sequence reads that passed quality filters were analyzed at the transcript isoform level with Hisat2, Trapnell, STAR. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: A total of 1020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. 8 exosomal lncRNAs were confirmed with qRT–PCR.The result showed that the expression trend of differential expressed lncRNAs in validation was consistent with RNA-seq.Conclusion: Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic potential for LAA stroke for the first time. The results suggested that exosomal lncRNA could be potential diagnostic tools in LAA stroke. Circular RNAs (circRNAs), novel endogenous noncoding RNAs, play diverse roles in ischemic stroke. Recently, the abundance and stability of circRNAs in exosomes have been identified. However, a comprehensive analysis of exosomal circRNAs in large artery atherosclerotic (LAA) stroke has not yet been reported. We performed RNA sequencing (RNA-Seq) to comprehensively identify differentially expressed exosomal circRNAs in five paired LAA and normal controls. RNA-Seq identified a total of 462 circRNAs in peripheral exosomes; there were 25 differentially expressed circRNAs among them. Additionally, circRNA competing endogenous RNA (ceRNA) network and translatable analysis revealed the potential functions of the exosomal circRNAs in LAA progression. Two ceRNA pathways involving 5 circRNAs, 2 miRNAs, and 3 mRNAs were confirmed by qRT-PCR. In the validation cohort, receiver operating characteristic (ROC) curve analysis identified two circRNAs as possible novel biomarkers, and a logistic model combining two and four circRNAs increased the area under the curve compared with the individual circRNAs.

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Exploration of differentially-expressed exosomal mRNAs, lncRNAs and circRNAs from serum samples of gallbladder cancer and xantho-granulomatous cholecystitis patients

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