Dataset Information

RNA-Seq Profiling of Serum Exosomal Circular RNAs Reveals Circ-PNN as a Potential Biomarker for Human Colorectal Cancer.

ABSTRACT: Circular RNAs (circRNAs) are emerging as cardinal areas of focus in the non-coding RNA field. Growing evidences have revealed exosomal circRNAs as potential biomarkers for detection of various cancers. However, the clinical importance of most serum exosomal circRNAs in colorectal cancer (CRC) have rarely been investigated. In this study, we examined the possible clinical application of serum exosomal circRNAs in the diagnosis of CRC. Firstly, we conducted RNA sequencing (RNA-seq) analysis using fifty CRC and fifty healthy control serum samples to identify CRC-related circRNAs. The sequencing data showed 122 differentially expressed circRNAs including 100 up-regulated and 22 down-regulated circRNA transcripts in CRC patients. Then, eight most dysregulated circRNAs were selected for validation by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. Validation analysis revealed that the serum exosomal circ-PNN (hsa_circ_0101802) levels were significantly up-regulated in CRC cases compared with those in the healthy control groups. Receiver operating characteristic curve (ROC) analysis suggested that circ-PNN had significant value in CRC diagnosis with areas under the ROC curve (AUC) of 0.855 and 0.826 in the training and validation sets, respectively. We also found that the AUC of serum exosomal circ-PNN for early-stage CRC was 0.854. Finally, a network map based on circ-PNN was constructed to determine its potential miRNA-mRNAs binding. We also demonstrated that the expression of hsa-miR-6833-3P, hsa-let-7i-3p and hsa-miR-1301-3P were negatively correlated with circ-PNN in CRC patients. Collectively, our findings indicated that serum exosomal circ-PNN might be a potential non-invasive biomarker for the detection of CRC and may play a crucial role in the pathogenesis of CRC.

SUBMITTER: Xie Y

PROVIDER: S-EPMC7314951 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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RNA-Seq Profiling of Serum Exosomal Circular RNAs Reveals Circ-PNN as a Potential Biomarker for Human Colorectal Cancer.

Xie Yan Y Li Juan J Li Peilong P Li Ning N Zhang Ying Y Binang Helen H Zhao Yinghui Y Duan Weili W Chen Yingjie Y Wang Yunshan Y Du Lutao L Wang Chuanxin C

Frontiers in oncology 20200618

Circular RNAs (circRNAs) are emerging as cardinal areas of focus in the non-coding RNA field. Growing evidences have revealed exosomal circRNAs as potential biomarkers for detection of various cancers. However, the clinical importance of most serum exosomal circRNAs in colorectal cancer (CRC) have rarely been investigated. In this study, we examined the possible clinical application of serum exosomal circRNAs in the diagnosis of CRC. Firstly, we conducted RNA sequencing (RNA-seq) analysis using ...[more]

PMID: 32626660

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Project description:Background: Exosomal circular RNAs (circRNAs) in peripheral blood are considered as emerging diagnostic biomarkers of cancers. Owing to the lack of sensitive and specific biomarkers, a large number of colorectal cancer (CRC) patients were diagnosed in advanced stages leading to high mortality. This study aimed to identify circulating exosomal circRNAs as novel diagnostic biomarkers of CRC. Materials and Methods: Candidate circRNA was selected by integrating analysis of Gene Expression Omnibus (GEO) database with online program GEO2R. A total of 170 patients and 45 healthy controls were enrolled to assess the diagnostic value of circRNAs for CRC. Exosomes isolated from the serum of participants and cell cultured media were confirmed by transmission electron microscope (TEM), Nanoparticle Tracking Analysis and western blot. The expression and the diagnostic utility of circRNA were tested by qRT-PCR and receiver operating characteristic (ROC) analysis, respectively. Results: The circulating exosomal hsa-circ-0004771 with most abundant among the top ten differentially expressed circRNAs (fold change ?1.5) was selected for further study based on the results of GEO dataset analysis. The up-regulated exosomal hsa-circ-0004771 was verified in serum of CRC patients compared to healthy controls (HCs) and patients with benign intestinal diseases (BIDs) by qRT-PCR. The area under the ROC curves (AUCs) of circulating exosomal hsa-circ-0004771 were 0.59 (95%CI, 0.457-0.725), 0.86 (95%CI, 0.785-0.933) and 0.88 (95%CI, 0.815-0.940) to differentiate BIDs, stage I/II CRC patients and CRC patients from HCs, respectively. The AUC was 0.816 (95%CI, 0.728-0.9) to differentiate stage I/II CRC patients from patients with BIDs. In addition, the elevated expression of exosomal hsa-circ-0004771 in the serum of CRC patients was tumor-derived. It was found that the expression of exosomal hsa-circ-0004771 was down-regulated expression of in the serum of postoperative CRC patients as well as cultured media of CRC cells treated with GW4869. Conclusions: Circulating exosomal hsa-circ-0004771 was significantly up-regulated in CRC patients and served as a novel potential diagnostic biomarker of CRC.

Project description:Abnormal expression of non-coding circular RNAs (circRNAs) have been reported in many types of tumors. circRNA have been suggested to be an ideal candidate biomarker for diagnostic and therapeutic implications in cancers. The aim of this study was to assess the circRNA expression profile of laryngeal squamous cell carcinomas (LSCC). The biopsy samples from patients with LSCC were obtained intra-operatively. The circRNA expression was performed using secondary sequencing. Among 10 patients with LSCC, 2 were well differentiated, 3 were moderately differentiated and 5 were adjunctive samples with normal and LSCC tissues. A total of 21,444 distinct circRNA candidates were detected. Among them, we defined the statistical criteria for selecting aberrant-expressed circRNA using a q-value of < 0.001 with a fold change of > 2.0 or < 0.5. A total of 29 circRNA were upregulated and 19 circRNA were downregulated significantly in the LSCC tissues. The intersection of these dysregulated circRNAs of normal-well differentiated set and normal-moderately differentiated set was then assessed to narrow the upregulated and downregulated circRNAs down to 18 and 5 respectively. Furthermore, an association of the circRNA-miRNA-mRNA was investigated, showing that 20 dysregulated circRNA successfully predicted an interaction with several cancer-related miRNAs. Finally, a further KEGG analysis showed that PPAR, Axon guidance, Wnt and Cell cycle signaling pathway were key putative pathways in the process of LSCC. hsa_circ:chr20:31876585-31,897,648 was found to be able to differentiate most of LSCC from the matching normal tissues. This observational study demonstrated dysregulation of circRNA in LSCC, which may have an impact on development of potential biomarkers in this disease. Validation of down-regulation of hsa_circ:chr20:31876585-31,897,648 in LSCC compared to each adjunctive tissue by Q-RT-PCR, indicating that hsa_circ:chr20:31876585-31,897,648 may be a novel promising tumor suppresser in LSCC.

Dataset Information

RNA-Seq Profiling of Serum Exosomal Circular RNAs Reveals Circ-PNN as a Potential Biomarker for Human Colorectal Cancer.

Publications

RNA-Seq Profiling of Serum Exosomal Circular RNAs Reveals Circ-PNN as a Potential Biomarker for Human Colorectal Cancer.

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