Abstract
BackgroundColorectal cancer (CRC) is a common malignant tumor with unsatisfactory overall prognosis. CircRNAs could be promising prognostic biomarkers in cancers, and play important role in the process of tumorigenesis and progression. Here, we explored the role of hsa_circ_0004831 in blood extracellular vesicles and its prognostic value in CRC.MethodsThe circRNA and mRNA expression level matrix in extracellular vesicles of CRC and normal samples were obtained from the exoRBase database. The corresponding miRNA expression level matrix in extracellular vesicles was downloaded from the BBCancer database. Differentially expressed circRNAs, miRNAs and mRNAs were identified using the limma package of R software at the cut-off criteria of fold change (FC) > 2 and adj. p < 0.05. RT-qPCR assay was conducted to measure hsa_circ_0004831 expression level in CRC blood samples. A circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on competitive endogenous RNA mechanism and differentially expressed genes. The mRNAs co-expressed with hsa_circ_0004831 were screened at the cut-off criteria of pearson |r| > 0.3 and p < 0.05. Gene set enrichment analysis (GSEA) based on co-expressed mRNAs was used to explore the potential molecular function of hsa_circ_0004831.ResultsDifferentially expressed circRNAs, miRNAs and mRNAs were identified and hsa_circ_0004831 had a FC value of 3.92 in CRC blood extracellular vesicles. The RT-qPCR assay showed that the hsa_circ_0004831 was up-regulated in CRC blood samples. The overall survival analysis found that high expression of hsa_circ_0004831 was linked with poorer prognosis. Finally, a circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on down-regulated miR-4326 and 12 up-regulated mRNAs. GSEA indicated that mRNAs co-expressed with hsa_circ_0004831 were involved in EMT, WNT and p53 signaling pathways.ConclusionsThe study confirmed the up-regulation of hsa_circ_0004831 in CRC, and it may act as a vital prognostic biomarker. The circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 could be used to uncover the tumorigenesis and progression of CRC.
Highlights
Colorectal cancer (CRC) is a common malignant tumor with unsatisfactory overall prognosis
The Kaplan– Meier analysis with log-rank test found that high expression of hsa_circ_0004831 was linked with poorer prognosis
Gene set enrichment analysis (GSEA) showed that mRNAs co-expressed with hsa_circ_0004831 were involved in Epithelialmesenchymal transition (EMT), WNT and p53 signaling pathways
Summary
Colorectal cancer (CRC) is a common malignant tumor with unsatisfactory overall prognosis. CircRNAs could be promising prognostic biomarkers in cancers, and play important role in the process of tumorigenesis and progression. The incidence of colorectal cancer (CRC) ranks the third among all human cancers in 2018 and is a common malignant tumor in the clinic [1, 2]. It is necessary to further elucidate the pathophysiological processes that occur in CRC and explore more efficient biomarkers in prognostic prediction. CircRNAs were characterized by a covalently closed-loop structures without 5’ and 3’ terminals and play vital role in the processes of various cancers progression [6, 7]. Extensive studies have revealed the vital importance of circRNAs in human diseases, including cancers [8,9,10]. The roles of a large number of circRNAs in CRC remain unclear
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