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Comprehensive Circular RNA Profiling Reveals That hsa_circ_0005075, a New Circular RNA Biomarker, Is Involved in Hepatocellular Crcinoma Development.

ABSTRACT: There is increasing evidence that circular RNAs (circRNAs) are involved in cancer development; however, their role in hepatocellular carcinoma (HCC) remains unclear. Here, we aimed to determine the circRNA expression profile in HCC, and investigate relevant mechanisms for cancer progression. The global circRNA expression profile between HCC (n?=?3) and adjacent normal liver (n?=?3) tissue was significantly different. Three circRNAs (hsa_circ_0000520, hsa_circ_0005075, and hsa_circ_0066444) showed significantly different expression levels in HCC tissues, which were further validated in 60 matched tissue samples using real-time qRT-PCR. Only hsa_circ_0005075 exhibited significant difference in expression (P?<0.001) between HCC and normal tissues. Hsa_circ_0005075 expression correlated with HCC tumor size (P?=?0.042), and showed good diagnostic potential (AUROC?=?0.94). Finally, we constructed a network of hsa_circ_0005075-targeted miRNA-gene interactions, including miR-23b-5p, miR-93-3p, miR-581, miR-23a-5p, and their corresponding mRNAs. Gene oncology analysis revealed that hsa_circ_0005075 could participate in cell adhesion during HCC development. In summary, we identified hsa_circ_0005075 as a potential HCC biomarker; however, further studies are required to confirm the role of this circRNA, and others, in HCC development.

SUBMITTER: Shang X

PROVIDER: S-EPMC4900729 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Comprehensive Circular RNA Profiling Reveals That hsa_circ_0005075, a New Circular RNA Biomarker, Is Involved in Hepatocellular Crcinoma Development.

Shang Xingchen X Li Guanzhen G Liu Hui H Li Tao T Liu Juan J Zhao Qi Q Wang Chuanxi C

Medicine 20160501 22

There is increasing evidence that circular RNAs (circRNAs) are involved in cancer development; however, their role in hepatocellular carcinoma (HCC) remains unclear. Here, we aimed to determine the circRNA expression profile in HCC, and investigate relevant mechanisms for cancer progression. The global circRNA expression profile between HCC (n = 3) and adjacent normal liver (n = 3) tissue was significantly different. Three circRNAs (hsa_circ_0000520, hsa_circ_0005075, and hsa_circ_0066444) showe ...[more]

PMID: 27258521

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Project description:Background: The morbidity and mortality of gastric cancer (GC) remain high worldwide. With the advent of the Human Genome Sequencing Project, circular RNAs (circRNAs) have attracted widespread attention in cancer research due to their stable ring structure. Our aim was to identify differentially expressed circRNAs in GC and explore their potential roles in GC diagnosis, treatment, and prognostic prediction. Methods: Large-scale gene screening was performed in three pairs of GC tissues and adjacent noncancerous tissues using high-throughput sequencing. The expression of hsa_circ_0001821 was detected in 80 pairs of tissue samples by quantitative real-time PCR (qRT-PCR). Stability of the ring structure of hsa_circ_0001821 RNA was verified by exonuclease digestion assay, and its diagnostic value was evaluated by receiver operating characteristic (ROC) analysis. In addition, the location of hsa_circ_0001821 in GC cells was detected by nucleoplasm separation assay. Results: A total of 25,303 circRNAs were identified, among which 2,007 circRNAs were differentially expressed (fold change > 2.0, P < 0.05). Further validation disclosed that hsa_circ_0001821 was significantly downregulated in the 80 pairs of GC tissues and 30 whole-blood specimens obtained from the GC patients. The specificity of hsa_circ_0001821 in GC was higher than that in other solid tumors. In addition, hsa_circ_0001821 was relatively stable after RNA exonuclease digestion. Clinicopathological parameter analysis showed that hsa_circ_0001821 was negatively correlated with tumor depth (r = -0.255, P = 0.022) and lymph node metastasis (r = -0.235, P = 0.036). Area under the curve (AUC) analysis showed that the diagnostic efficiency of circulating hsa_circ_0001821 in distinguishing GC patients was higher than that in GC tissues (0.872, 95%CI: 0.767-0.977 vs. 0.792, 95%CI: 0.723-0.861). Combined use of circulating hsa_circ_0001821 with the existing tumor markers yielded the largest AUC of 0.933. Finally, hsa_circ_0001821 was demonstrated to mainly locate in the cytoplasm, implying that it played a potential regulatory role in GC at the posttranscriptional level. Conclusion: Hsa_circ_0001821 may prove to be a new and promising potential biomarker for GC diagnosis.

Project description:BackgroundLiver cirrhosis is a well-known risk factor for hepatocellular carcinoma (HCC). However, some HCC cases can also originate from non-cirrhotic livers. The aim of this study was to identify key circular RNAs (circRNAs) associated with the tumorigenesis of non-cirrhotic liver disease.MethodsThe differently expressed circRNAs between non-cirrhotic and cirrhotic HCCs were assessed with use of high-throughput circRNAs sequencing and validated with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Potential biological functions of these dysregulated circRNAs were predicted with use of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A circRNA-miRNA-mRNA regulation network was constructed as achieved with use of miRanda software and visualized using Cytoscape software. Biological functions of the four most prominent dysregulated circRNAs identified were confirmed by in vitro experiments. Moreover, possible translations of these dysregulated circRNAs were also predicted.ResultsA total of 393 dysregulated circRNAs were identified between non-cirrhotic and cirrhotic HCC, including 213 that were significantly up-regulated and 180 significantly down-regulated circRNAs. Expression levels of the six most prominent dysregulated circRNAs were further validated using qRT-PCR. Many tumor related miRNAs were involved in the circRNA-miRNA-mRNA networks, including miR-182-5p, miR-561-3p, miR-125a-5p, miR-145, miR-23b-3p and miR-30e-3p, and downstream mRNAs of dysregulated circRNAs were significantly related with biological processes involved in the progression of tumors, including proliferation, migration, differentiation, and focal adhesion. Results from the in vitro experiments demonstrated that the most prominent dysregulated circRNAs exerted notable effects upon the proliferation and migration of HCC cells. Finally, we also identified 19 dysregulated circRNAs having potential for the coding of functional peptides.ConclusionThe results of this present study indicate that circRNAs may play important roles in tumorigenesis of non-cirrhotic HCC. Such findings provide some novel insights and pave the way for the development of future studies directed at investigating the initiation and treatment of HCC.

Dataset Information

Comprehensive Circular RNA Profiling Reveals That hsa_circ_0005075, a New Circular RNA Biomarker, Is Involved in Hepatocellular Crcinoma Development.

Publications

Comprehensive Circular RNA Profiling Reveals That hsa_circ_0005075, a New Circular RNA Biomarker, Is Involved in Hepatocellular Crcinoma Development.

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