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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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      Expression and clinical significance of the long non-coding RNA PVT1 in human gastric cancer

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          Abstract

          Background

          Highly sensitive markers are urgently needed for the diagnosis and grading of gastric cancer and for managing drug resistance. The recent identification of long-non-coding RNAs (lncRNAs) has provided new approaches for resolving this challenge. The aim of this study was to screen and identify new biomarkers for human gastric cancer from lncRNAs.

          Methods

          First, we used lncRNA microarrays to conduct a preliminary screening for candidate lncRNAs of gastric cancer biomarkers in both human gastric cancer tissues and in two gastric cancer cell lines, SGC7901 cells and paclitaxel-resistant SGC7901 cells. The lncRNA plasma-cytoma variant translocation 1 ( PVT1) was found to exhibit higher expression in both gastric cancer tissues and the SGC7901 paclitaxel-resistant cell line. Quantitative polymerase chain reaction was used for large-scale analysis in a large number of human gastric cancer tissues to verify the involvement of PVT1 in development of gastric cancer. The relationships between PVT1 expression and clinical features were also analyzed.

          Results

          PVT1 showed higher expression in human gastric cancer tissues than in adjacent non-cancerous tissues and in SGC7901 paclitaxel-resistant cells compared with SGC7901 cells. PVT1 expression was correlated with lymph node invasion of gastric cancer.

          Conclusion

          PVT1 is a new biomarker for human gastric cancer and may indicate lymph node invasion. Therefore, PVT1 shows potential as a novel therapeutic target for the treatment of gastric cancer and enhancement of paclitaxel sensitivity.

          Most cited references15

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          A small cell lung cancer genome reports complex tobacco exposure signatures

          SUMMARY Cancer is driven by mutation. Worldwide, tobacco smoking is the major lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. 22,910 somatic substitutions were identified, including 132 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in-frame, and another two lines carrying PVT1-CHD7 fusion genes, suggesting that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.
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            Epigenetic activation of the MiR-200 family contributes to H19-mediated metastasis suppression in hepatocellular carcinoma.

            Although numerous long non-coding RNAs (lncRNAs) have been identified in mammals, many of their biological roles remain to be characterized. Early reports suggest that H19 contributes to carcinogenesis, including hepatocellular carcinoma (HCC). Examination of the Oncomine resource showed that most HCC cases express H19 at a level that is comparable with the liver, with a tendency toward lower expression. This is consistent with our previous microarray data and indicates a more complicated role of H19 in HCC that needs to be characterized. In this study, the expression level of H19 was assessed in different regions of HCC patients' liver samples. Loss- and gain-of-function studies on this lncRNA in the HCC cell lines, SMMC7721 and HCCLM3, were used to characterize its effects on gene expression and to assess its effect on HCC metastasis both in vitro and in vivo. In this study, we show that H19 was underexpressed in intratumoral HCC tissues (T), as compared with peritumoral tissues (L). Additionally, low T/L ratio of H19 predicted poor prognosis. H19 suppressed HCC progression metastasis and the expression of markers of epithelial-to-mesenchymal transition. Furthermore, H19 associated with the protein complex hnRNP U/PCAF/RNAPol II, activating miR-200 family by increasing histone acetylation. The results demonstrate that H19 can alter the miR-200 pathway, thus contributing to mesenchymal-to-epithelial transition and to the suppression of tumor metastasis. These data provide an explanation for the hitherto puzzling literature on the relationship between H19 and cancer, and could suggest the development of combination therapies that target H19 and the miR-200 family.
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              International variation.

              D Parkin (2004)
              There were an estimated 10 million new cases, 6 million deaths and 22 million persons living with cancer in the year 2000. The most common cancers are, in terms of new cases, lung (1.2 million), breast (1.05 million), colon-rectum (945 000), stomach (876 000) and liver (564 000). The geographic distributions of some 20 types of cancer for which national estimates have been made are summarized. These patterns are examined with respect to the likely reasons in terms of variation in exposure to carcinogens (in the external environment or through lifestyle choices) or in genetic susceptibility to them. Related data from studies of migrant populations (that allow comparisons of genetically similar populations living in different environments) and from comparisons between different ethnic groups living in the same country are used to help in the interpretation of the geographic patterns. Information on the burden of disease also has a very important role in the planning and monitoring of programmes of cancer control.
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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
                2014
                18 September 2014
                : 7
                : 1625-1630
                Affiliations
                [1 ]Digestive Department of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
                [2 ]Digestive Department of Union Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
                Author notes
                Correspondence: Jian Ding, Digestive Department of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China, Email docdingjian@ 123456163.com

                *These authors contributed equally to this work

                Article
                ott-7-1625
                10.2147/OTT.S68854
                4172193
                25258543
                f82bf04a-7dbe-478f-83ee-22376b3af40e
                © 2014 Ding et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. 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
                microarray analysis,quantitative polymerase chain reaction,lymph node invasion,tumor biomarkers,paclitaxel resistance

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