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

BackgroundLong 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.MethodsThe 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.ResultsTotal 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.ConclusionsThe 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.

[1]  M. Toyota,et al.  Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. , 2012, Cancer research.

[2]  S. Miyano,et al.  Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. , 2011, Cancer research.

[3]  Junming Guo,et al.  Up-regulation of SUMO1 pseudogene 3 (SUMO1P3) in gastric cancer and its clinical association , 2013, Medical Oncology.

[4]  Bangshun He,et al.  Analysis of long non-coding RNA expression profiles in gastric cancer. , 2013, World journal of gastroenterology.

[5]  Paulo P. Amaral,et al.  Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. , 2008, Genome research.

[6]  Feng Yang,et al.  Up‐regulated long non‐coding RNA H19 contributes to proliferation of gastric cancer cells , 2012, The FEBS journal.

[7]  M. Babjuk,et al.  Differential display code 3 (DD3/PCA3) in prostate cancer diagnosis. , 2010, Anticancer research.

[8]  K. Zatloukal,et al.  Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. , 2007, Gastroenterology.

[9]  Xinjun Zhang,et al.  Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker , 2010, Journal of Molecular Medicine.

[10]  A. Gabory,et al.  The H19 locus acts in vivo as a tumor suppressor , 2008, Proceedings of the National Academy of Sciences.

[11]  A. Hochberg,et al.  The H19 Non-Coding RNA Is Essential for Human Tumor Growth , 2007, PloS one.

[12]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[13]  Howard Y. Chang,et al.  Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis , 2010, Nature.

[14]  P. Hall,et al.  New perspectives on neoplasia and the RNA world , 2005, Hematological oncology.

[15]  S. French,et al.  The regulation of non-coding RNA expression in the liver of mice fed DDC. , 2009, Experimental and molecular pathology.

[16]  Howard Y. Chang,et al.  Long noncoding RNAs and human disease. , 2011, Trends in cell biology.

[17]  J. Mattick,et al.  Protein-coding and non-coding gene expression analysis in differentiating human keratinocytes using a three-dimensional epidermal equivalent , 2010, Molecular Genetics and Genomics.

[18]  Zhen Jiang,et al.  Increased expression of miR-421 in human gastric carcinoma and its clinical association , 2009, Journal of Gastroenterology.

[19]  Michael Thomas,et al.  MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer , 2003, Oncogene.

[20]  M. Esteller.  Non-coding RNAs in human disease , 2011, Nature Reviews Genetics.

[21]  Q. Li,et al.  Large Intervening Non-Coding RNA HOTAIR is Associated with Hepatocellular Carcinoma Progression , 2011, The Journal of international medical research.

[22]  Wei Chen,et al.  The diagnostic value of PCA3 gene-based analysis of urine sediments after digital rectal examination for prostate cancer in a Chinese population. , 2011, Experimental and molecular pathology.

[23]  Andrew P Feinberg,et al.  Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects. , 2002, American journal of human genetics.

[24]  Ke Ma,et al.  LARP7 is a potential tumor suppressor gene in gastric cancer , 2012, Laboratory Investigation.

[25]  C. Kang,et al.  LncRNA profile of glioblastoma reveals the potential role of lncRNAs in contributing to glioblastoma pathogenesis. , 2012, International journal of oncology.

[26]  P. Lu,et al.  Loss of imprinting of insulin-like growth factor 2 is associated with increased risk of lymph node metastasis and gastric corpus cancer , 2009, Journal of experimental & clinical cancer research : CR.

[27]  M. Karin,et al.  A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas , 2007, Oncogene.

[28]  J. Pearson,et al.  The MUC2 gene product: a human intestinal mucin. , 1998, The international journal of biochemistry & cell biology.

[29]  T. Xia,et al.  Decreased expression of long noncoding RNA AC096655.1-002 in gastric cancer and its clinical significance , 2013, Tumor Biology.

[30]  P. Harrison,et al.  Mining Mammalian Transcript Data for Functional Long Non-Coding RNAs , 2010, PloS one.

[31]  F. Zhang,et al.  Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation , 2012, Medical Oncology.

[32]  B. Xiao,et al.  Differential expression of microRNA species in human gastric cancer versus non‐tumorous tissues , 2009, Journal of gastroenterology and hepatology.

[33]  M. Lotfy,et al.  MUC2 and MUC6 apomucins expression in human gastric neoplasm: an immunohistochemical analysis , 2011, Medical oncology.

[34]  Abraham Hochberg,et al.  Highly upregulated in liver cancer noncoding RNA is overexpressed in hepatic colorectal metastasis , 2009, European journal of gastroenterology & hepatology.