29-31 In the present study, we identified the differential expression profile of mRNA and circRNA in 3 pairs of liver cancer clinical specimens with use of circRNA and mRNA microarray detection. Recent research has revealed aberrant expression of several circRNAs in colorectal cancer (CRC), 21-23 gastric cancer (GC) 24-26 and Alzheimer disease (AD) 27, 28 however, the expression profiles of circRNAs in liver cancer tissues are not well characterized.
16-20 These findings indicate the potential regulatory role of circRNAs in biologic development, and in pathogenesis and progression of diseases.
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These features confer numerous potential functions to circRNAs, such as transcription regulators 15 or as competing endogenous RNAs to bind miRNAs (RNA sponges) or as RNA binding proteins (protein sponges), which helps these circRNAs modulate their local free concentration. 14 Because of the lack of free ends, circRNAs are resistant to exonucleases, which help these circRNAs escape the normal RNA turnover.
10-13 Thanks to the technological breakthroughs in high-throughput deep sequencing, single-stranded circular RNAs are no longer perceived as splicing errors and are gradually assumed as the center stage in cancer genomics research. 7-9 It is thus necessary to identify molecular targets and novel pathways that underlie tumorigenesis and progression of liver cancer.Ĭircular RNAs (circRNAs), are kinds of special endogenous ncRNAs that are predominantly generated by a process called ‘back-splicing’, followed by formation of covalently-closed continuous loops. 6 Although the survival rate of patients with liver cancer has improved, most patients who undergo surgical resection experience metatases and recurrence within 5 years. 5 According to World Health Organization (WHO), liver cancer accounted for 9% of all cancer-related deaths worldwide in 2012. 1-4 More than 700,000 cases of liver cancer were diagnosed in 2008. Liver cancer is the sixth most prevalent cancer and the third most frequent cause of cancer-related deaths. Our results suggest the circRNA-miRNA-mRNA network may help us further understand the molecular mechanisms of tumor progression in liver cancer, and reveal novel biomarkers and therapeutic targets. ROC analysis showed circZFR, circFUT8, circIPO11 could significantly distinguish the cancer samples, with an AUC of 0.7069, 0.7575, and 0.7103, respectively. Quantitative real-time PCR was performed to verify the top-five circRNAs. We enriched the pathways and gene ontology items and determined their participation in cancer-related pathways such as p53 signaling pathway and pathways involved in angiogenesis and cell cycle. We selected the top-5 upregulated circRNAs to construct a circRNA-miRNA-mRNA network. We detected a total of 127 differentially expressed circRNAs and 3,235 differentially expressed mRNAs. In this study, we used a systems biology approach to construct and analyze the circRNA molecular regulatory networks in the context of liver cancer. Circular RNAs (circRNAs), a kind of special endogenous ncRNAs, have been coming back to the forefront of cancer genomics research. Liver cancer is the sixth most prevalent cancer, and the third most frequent cause of cancer-related deaths.
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