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      Long non-coding RNA expression profile in human gastric cancer and its clinical significances

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          Abstract

          Background

          Long non-coding RNAs (lncRNAs) are prevalently transcribed in the genome yet their potential roles in human cancers are not well understood. The aim of the present study was to determine the lncRNA expression profile in gastric cancer and its potential clinical value.

          Methods

          The global lncRNA expression profile in gastric cancer was measured by lncRNA microarray. Levels of two representative lncRNAs, H19 and uc001lsz, were confirmed by real-time reverse transcriptase-polymerase chain reaction. The relationship between their levels and clinicopathological factors of patients with gastric cancer was explored. A receiver operating characteristic (ROC) curve was constructed for differentiating gastric cancer from benign gastric diseases.

          Results

          Total of 135 lncRNAs, which differential expression levels between tumor and non-tumorous tissues were more than twofold, were found (GEO No. GSE47850). The most down-regulated lncRNAs in gastric cancer tissues were FER1L4, uc001lsz, BG491697, AF131784, uc009ycs, BG981369, AF147447, HMlincRNA1600, and AK054588; while the most up-regulated ones were H19, HMlincRNA717, BM709340, BQ213083, AK054978, and DB077273. H19 was found highly expressed in stomach and liver cancer cell lines, while lowly expressed in lung cancer and prostate cancer cell lines. Uc001lsz was lowly expressed in gastric, lung and liver cancer cell lines, while highly expressed in prostate cancer. The areas under ROC curves were up to 0.613, 0.751, and 0.761 for H19, uc001lsz, and the combination, respectively.

          Conclusions

          The lncRNA expression profile in gastric cancer suggests the potential roles of lncRNAs in gastric cancer occurrence and development. The overexpression of H19 in gastric cancer suggests that H19 may be participated in gastric cancer. The reduced expression of uc001lsz in gastric cancer cell lines and tissues, its associations with TNM stage, and its dysregulation in early cancer and precancerous lesions suggest that uc001lsz may be a potential marker for the diagnosis of early gastric cancer.

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          Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells.

          Feng Yang, Jianwei Bi, Xuchao Xue … (2012)
          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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            Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors.

            Takeshi Niinuma, Hiromu Suzuki, Masanori Nojima … (2012)
            Large intergenic noncoding RNAs (lincRNA) have been less studied than miRNAs in cancer, although both offer considerable theranostic potential. In this study, we identified frequent upregulation of miR-196a and lincRNA HOTAIR in high-risk gastrointestinal stromal tumors (GIST). Overexpression of miR-196a was associated with high-risk grade, metastasis and poor survival among GIST specimens. miR-196a genes are located within the HOX gene clusters and microarray expression analysis revealed that the HOXC and HOTAIR gene were also coordinately upregulated in GISTs which overexpress miR-196a. In like manner, overexpression of HOTAIR was also strongly associated with high-risk grade and metastasis among GIST specimens. RNA interference-mediated knockdown of HOTAIR altered the expression of reported HOTAIR target genes and suppressed GIST cell invasiveness. These findings reveal concurrent overexpression of HOX genes with noncoding RNAs in human cancer in this setting, revealing miR-196a and HOTAIR as potentially useful biomarkers and therapeutic targets in malignant GISTs.
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              Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues.

              Bingxiu Xiao, Junming Guo, Yanjun Wang … (2009)
              MicroRNAs (miRNAs) play important roles in carcinogenesis. The global miRNA expression profile of gastric cancer has not been reported. The purpose of the present study was to determine the miRNA expression profile of gastric cancer. Total RNA were first extracted from primary gastric cancer tissues and adjacent non-tumorous tissues and then small isolated RNAs (< 300 nt) were 3'-extended with a poly(A) tail. Hybridization was carried out on a microParaflo microfluidic chip (LC Sciences, Houston, TX, USA). After hybridization detection by fluorescence labeling using tag-specific Cy3 and Cy5 dyes, hybridization images were collected using a laser scanner and digitized using Array-Pro image analysis software (Media Cybernetics, Silver Spring, MD, USA). To validate the results and investigate the biological meaning of differential expressed miRNAs, immunohistochemistry was used to detect the differential expression of target genes. The most highly expressed miRNAs in non-tumorous tissues were miR-768-3p, miR-139-5p, miR-378, miR-31, miR-195, miR-497 and miR-133b. Three of them, miR-139-5p, miR-497 and miR-768-3p, were first found in non-tumorous tissues. The most highly expressed miRNAs in gastric cancer tissues were miR-20b, miR-20a, miR-17, miR-106a, miR-18a, miR-21, miR-106b, miR-18b, miR-421, miR-340*, miR-19a and miR-658. Among them, miR-340*, miR-421 and miR-658 were first found highly expressed in cancer cells. The expression of some target genes (such as Rb and PTEN) in cancer tissues was found to be decreased. To our knowledge, this is the first report about these miRNAs associated with gastric cancer. This new information may suggest the potential roles of these miRNAs in the diagnosis of gastric cancer.
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                Author and article information

                Contributors
                Haojun Song
                Weiliang Sun
                Guoliang Ye
                Xiaoyun Ding
                Zhong Liu
                Sijie Zhang
                Tian Xia
                Bingxiu Xiao
                Yang Xi
                Junming Guo
                Journal
                Journal ID (nlm-ta): J Transl Med
                Journal ID (iso-abbrev): J Transl Med
                Title: Journal of Translational Medicine
                Publisher: BioMed Central
                ISSN (Electronic): 1479-5876
                Publication date Collection: 2013
                Publication date (Electronic): 24 September 2013
                Volume: 11
                Page: 225
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology, and Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
                [2 ]Ningbo Yinzhou People’s Hospital and the Affiliated Hospital, Ningbo University School of Medicine, Ningbo 315040, China
                [3 ]The Affiliated Hospital, Ningbo University School of Medicine, Ningbo 315010, China
                [4 ]Ningbo No. 1 Hospital and the Affiliated Hospital, Ningbo University School of Medicine, Ningbo 315010, China
                Article
                Publisher ID: 1479-5876-11-225
                DOI: 10.1186/1479-5876-11-225
                PMC ID: 3848969
                PubMed ID: 24063685
                SO-VID: 5c94e60e-5bb8-4ffa-80d9-80a9c38230f9
                Copyright © Copyright © 2013 Song et al.; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 24 August 2013
                Date accepted : 18 September 2013
                Categories
                Subject: Research

                ScienceOpen disciplines: Medicine
                Keywords: gastric cancer,long non-coding rna,expression profile,h19,uc001lsz
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: gastric cancer, long non-coding rna, expression profile, h19, uc001lsz

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