Abstract
BackgroundCircular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed.MethodsCircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA–miRNA–mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs.ResultsTotally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis.ConclusionIn conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.
Highlights
Circular RNAs, a novel type of noncoding RNAs, play critical roles in the initiation and pro‐ gression of cancer
Despite the early diagnosis and treatment of CRC developed in recent years, the 5-year survival rate for colorectal cancer is still not satisfactory, mainly because most patients are diagnosed with distant metastasis or at an advanced stage
As depicted by the volcano plot, our results indicated that of the 204 circRNAs differentially expressed between the CRC and normal plasma (P < 0.05), 26 were downregulated, while 178 were up-regulated in CRC plasma (Fig. 2a)
Summary
Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and pro‐ gression of cancer. Emerging studies shows that circRNAs may function as potential markers for cancer diagnosis and treatment. The diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed. Despite the early diagnosis and treatment of CRC developed in recent years, the 5-year survival rate for colorectal cancer is still not satisfactory, mainly because most patients are diagnosed with distant metastasis or at an advanced stage [2]. In the field of early diagnosis, novel biomarkers of CRC with high sensitivity and specificity are eagerly needed. Circular RNAs (circRNAs), which are a type of RNAs closely looped with no accessible ends, are the downstream products of precursor mRNA back-splicing of a huge amount of eukaryotic genes [3]. CircRNAs display a higher cell and tissue specificity, and their closed structure is more stable than lncRNAs and miRNAs, suggesting that they may serve as potential molecular
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