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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Upregulated long intergenic noncoding RNA KRT18P55 acts as a novel biomarker for the progression of intestinal-type gastric cancer

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          Abstract

          Background

          Long noncoding RNAs (lncRNAs) with dysregulated expression levels have been investigated in numerous types of different cancer. Whether lncRNAs can predict the progression of gastric cancer (GC) still remains largely unclear. The aim of our study was to investigate whether KRT18P55, a novel intergenic lncRNA, can be a predictive biomarker for GC.

          Methods

          To determine the expression levels of KRT18P55 in GC, we evaluated it in five GC cell lines (SGC-7901, MGC-803, BGC-823, AGS, and HG27) and 97 GC tissue samples in comparison with a normal control by quantitative polymerase chain reaction. In addition, the association with patient clinicopathological characteristics was analyzed to identify the clinical significance of KRT18P55. We also used publicly accessible data from The Cancer Genome Atlas (TCGA) to further verify the expression levels and clinical significance of KRT18P55. Furthermore, a receiver operating characteristic curve was also conducted to evaluate the diagnostic value of KRT18P55 for GC.

          Results

          A significant upregulation was observed in GC cell lines ( P<0.01) and tissue samples ( P<0.01). This finding was consistent with the results of 29 pairs of GC tissue samples from TCGA ( P<0.01). Additionally, we indicated that the increased expression of KRT18P55 was related to the progression of intestinal type ( P=0.032), which was also supported by results of independent GC cohorts from TCGA ( P<0.01). However, we did not find significant difference in prognosis between patients with high and low expression of KRT18P55 ( P>0.05). Finally, KRT18P55 showed potential diagnostic value for GC with an area under the receiver operating characteristic curve of 0.733 ( P<0.01).

          Conclusion

          Upregulated KRT18P55 was a novel biomarker for the progression of GC, especially for the intestinal type.

          Most cited references30

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          The Genetic Signatures of Noncoding RNAs

          The majority of the genome in animals and plants is transcribed in a developmentally regulated manner to produce large numbers of non–protein-coding RNAs (ncRNAs), whose incidence increases with developmental complexity. There is growing evidence that these transcripts are functional, particularly in the regulation of epigenetic processes, leading to the suggestion that they compose a hitherto hidden layer of genomic programming in humans and other complex organisms. However, to date, very few have been identified in genetic screens. Here I show that this is explicable by an historic emphasis, both phenotypically and technically, on mutations in protein-coding sequences, and by presumptions about the nature of regulatory mutations. Most variations in regulatory sequences produce relatively subtle phenotypic changes, in contrast to mutations in protein-coding sequences that frequently cause catastrophic component failure. Until recently, most mapping projects have focused on protein-coding sequences, and the limited number of identified regulatory mutations have been interpreted as affecting conventional cis-acting promoter and enhancer elements, although these regions are often themselves transcribed. Moreover, ncRNA-directed regulatory circuits underpin most, if not all, complex genetic phenomena in eukaryotes, including RNA interference-related processes such as transcriptional and post-transcriptional gene silencing, position effect variegation, hybrid dysgenesis, chromosome dosage compensation, parental imprinting and allelic exclusion, paramutation, and possibly transvection and transinduction. The next frontier is the identification and functional characterization of the myriad sequence variations that influence quantitative traits, disease susceptibility, and other complex characteristics, which are being shown by genome-wide association studies to lie mostly in noncoding, presumably regulatory, regions. There is every possibility that many of these variations will alter the interactions between regulatory RNAs and their targets, a prospect that should be borne in mind in future functional analyses.
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            Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells.

            Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA H19 is up-regulated in hypoxic stress and in some tumors. However, the contributions of H19 to gastric cancer remain largely unknown. In this study, we assayed the H19 expression level in gastric cancer tissues by real-time PCR, and defined the biological functions by flow cytometry and RNA immunoprecipitation. We demonstrated that H19 levels were markedly increased in gastric cancer cells and gastric cancer tissues compared with normal controls. Moreover, ectopic expression of H19 increased cell proliferation, whereas H19 siRNA treatment contributed to cell apoptosis in AGS cell line. We further verified that H19 was associated with p53, and that this association resulted in partial p53 inactivation. These data suggest an important role for H19 in the molecular etiology of gastric cancer and potential application of H19 in gastric cancer therapy. © 2012 The Authors Journal compilation © 2012 FEBS.
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              Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer

              Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are regarded as useful tools for cancer detection, particularly for the early stage; however, little is known about their diagnostic impact on gastric cancer (GC). We hypothesized that GC-related lncRNAs might release into the circulation during tumor initiation and could be utilized to detect and monitor GC. 8 lncRNAs which previously found to be differently expressed in GC were selected as candidate targets for subsequent circulating lncRNA assay. After validating in 20 pairs of tissues and plasma in training set, H19 was selected for further analysis in another 70 patients and 70 controls. Plasma level of H19 was significantly higher in GC patients compared with normal controls (p < 0.0001). By receiver operating characteristic curve (ROC) analysis, the area under the ROC curve (AUC) was 0.838; p < 0.001; sensitivity, 82.9%; specificity, 72.9%). Furthermore, H19 expression enabled the differentiation of early stage GC from controls with AUC of 0.877; sensitivity, 85.5%; specificity, 80.1%. Besides, plasma levels of H19 were significantly lower in postoperative samples than preoperative samples (p = 0.001). In conclusion, plasma H19 could serve as a potential biomarker for diagnosis of GC, in particular for early tumor screening.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2016
                21 January 2016
                : 9
                : 445-453
                Affiliations
                Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, People’s Republic of China
                Author notes
                Correspondence: Zhenning Wang, Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, North Nanjing Street 155, Shenyang 110001, People’s Republic of China, Tel +86 24 8328 3556, Fax +86 24 2270 3578, Email josieon826@ 123456sina.cn
                [*]

                These authors contributed equally to this work

                Article
                ott-9-445
                10.2147/OTT.S98613
                4727520
                26855593
                493e92d6-0d61-4d28-acc1-37ae7c763b49
                © 2016 Ma et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Oncology & Radiotherapy
                biomarker,gastric cancer,intestinal type,krt18p55,long noncoding rna
                Oncology & Radiotherapy
                biomarker, gastric cancer, intestinal type, krt18p55, long noncoding rna

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