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      Circular RNA circ-LDLRAD3 as a biomarker in diagnosis of pancreatic cancer

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          Abstract

          AIM

          To analyze the diagnostic value of a circular RNA (circRNA), circ-LDLRAD3, in pancreatic cancer.

          METHODS

          Expression levels of circ-LDLRAD3 were tested in both cells and clinical samples; the latter included 30 paired pancreatic cancer tissues and adjacent non-tumorous tissues, 31 plasma samples from patients with pancreatic cancer, and 31 plasma samples from healthy volunteers. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to measure expression levels of circ-LDLRAD3 in cells and clinical samples; then, the relationship between clinicopathological factors of patient samples and expression of circ-LDLRAD3 in pancreatic cancer was analyzed. The diagnostic value of circ-LDLRAD3 was verified by receiver operating characteristic (ROC) curve analysis.

          RESULTS

          Circ-LDLRAD3 was up-regulated in pancreatic cancer cell lines ( P < 0.01), pancreatic cancer tissues ( P < 0.01), and plasma samples from patients with pancreatic cancer ( P < 0.01). High expression of circ-LDLRAD3 was significantly associated with venous invasion, lymphatic invasion, and metastasis. The area under the ROC curve of circ-LDLRAD3 alone or combination with CA19-9 was 0.67 and 0.87, respectively, with a sensitivity and specificity of 0.5738 (alone) and 0.7049 (alone), and 0.8033 (combination) and 0.9355 (combination), respectively.

          CONCLUSION

          These data suggest that circ-LDLRAD3 may be a biomarker in the diagnosis of pancreatic cancer.

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          Most cited references23

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          Circ2Traits: a comprehensive database for circular RNA potentially associated with disease and traits

          Circular RNAs are new players in regulation of post transcriptional gene expression. Animal genomes express many circular RNAs from diverse genomic locations. A recent study has validated a fairly large number of circular RNAs in human, mouse, and nematode. Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Their interaction with disease associated miRNAs indicates that circular RNAs are important for disease regulation. In this paper we studied the potential association of circular RNAs (circRNA) with human diseases in two different ways. Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated. For the miRNAs associated with individual diseases, we constructed a network of predicted interactions between the miRNAs and protein coding, long non-coding and circular RNA genes. We carried out gene ontology (GO) enrichment analysis on the set of protein coding genes in the miRNA- circRNA interactome of individual diseases to check the enrichment of genes associated with particular biological processes. Secondly, disease associated SNPs were mapped on circRNA loci, and Argonaute (Ago) interaction sites on circular RNAs were identified. We compiled a database of disease-circRNA association in Circ2Traits (http://gyanxet-beta.com/circdb/), the first comprehensive knowledgebase of potential association of circular RNAs with diseases in human.
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            Enhancer Reprogramming Promotes Pancreatic Cancer Metastasis.

            Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies, owing in part to its propensity for metastasis. Here, we used an organoid culture system to investigate how transcription and the enhancer landscape become altered during discrete stages of disease progression in a PDA mouse model. This approach revealed that the metastatic transition is accompanied by massive and recurrent alterations in enhancer activity. We implicate the pioneer factor FOXA1 as a driver of enhancer activation in this system, a mechanism that renders PDA cells more invasive and less anchorage-dependent for growth in vitro, as well as more metastatic in vivo. In this context, FOXA1-dependent enhancer reprogramming activates a transcriptional program of embryonic foregut endoderm. Collectively, our study implicates enhancer reprogramming, FOXA1 upregulation, and a retrograde developmental transition in PDA metastasis.
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              Pancreatic cancer biology and genetics from an evolutionary perspective.

              Cancer is an evolutionary disease, containing the hallmarks of an asexually reproducing unicellular organism subject to evolutionary paradigms. Pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer) is a particularly robust example of this phenomenon. Genomic features indicate that pancreatic cancer cells are selected for fitness advantages when encountering the geographic and resource-depleted constraints of the microenvironment. Phenotypic adaptations to these pressures help disseminated cells to survive in secondary sites, a major clinical problem for patients with this disease. In this Review we gather the wide-ranging aspects of pancreatic cancer research into a single concept rooted in Darwinian evolution, with the goal of identifying novel insights and opportunities for study.
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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                21 December 2017
                21 December 2017
                : 23
                : 47
                : 8345-8354
                Affiliations
                Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
                Medical Research Center, Shengjing Hospital of China Medical University, Benxi 117000, Liaoning Province, China
                Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
                Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
                Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
                Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
                Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
                Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
                Endoscopy Center, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China. sun-siyu@ 123456163.com
                Author notes

                Author contributions: Yang F and Sun SY were involved in the study conception and design; Yang F drafted the article and analyzed and interpreted the data; Guo JT and Ge N performed critical revision of the article for important intellectual content and collected the data; Liu X performed statistical analysis; Zhu P and Wang S conducted the evaluation of TNM stage of pancreatic cancer; all authors performed the final approval of the article.

                Correspondence to: Si-Yu Sun, MD, PhD, Chief, Professor, Endoscopy Center, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang 110004, Liaoning Province, China. sun-siyu@ 123456163.com

                Telephone: +86-24-96615-26111 Fax: +86-24-23892617

                Article
                jWJG.v23.i47.pg8345
                10.3748/wjg.v23.i47.8345
                5743505
                29307994
                94b25efd-305f-451f-96c5-5b67bca62e39
                ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 3 November 2017
                : 17 November 2017
                : 27 November 2017
                Categories
                Basic Study

                circular rna,pancreatic cancer,biomarker
                circular rna, pancreatic cancer, biomarker

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