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Published in: Tumor Biology 10/2015

01-10-2015 | Research Article

Invasion and metastasis-related long noncoding RNA expression profiles in hepatocellular carcinoma

Authors: Yunzhen Gao, Geng Chen, Yongyi Zeng, Jinhua Zeng, Minjie Lin, Xiaolong Liu, Jingfeng Liu

Published in: Tumor Biology | Issue 10/2015

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Abstract

Recurrence, invasion, and metastasis are the major reasons of the low 5-year survival of hepatocellular carcinoma. However, the mechanisms of recurrence, invasion, and metastasis are still poll understood. Long noncoding RNAs (LncRNAs, >200 nt) have been demonstrated to play important roles in both tumor suppressive and oncogenic signaling pathways. Here, we employed the LncRNAs microarray technology to study the LncRNAs expression profiles at genome-wide in hepatocellular carcinoma (HCC) tissue samples with early recurrence (less than 1 year, with invasion and metastasis out of liver) and late recurrence (longer than 2 years, without invasion and metastasis out of liver), which had different recurrent/metastatic potentials, by using normal liver tissue as control to screen the dysregulated LncRNAs which are potentially involved in the recurrence, invasion, and metastasis process of HCC. Overall, 1170 LncRNAs were identified to differentially expressed between the early and late recurrence samples. These differentially expressed LncRNAs were further characterized by integrating examination of genomic context, co-expression network analysis, and gene ontology (GO) enrichment of their associated protein-coding genes. Furthermore, 15 LncRNAs selected randomly from top 50 differentially expressed LncRNAs were validated by quantitative PCR (qPCR) in cell lines MHCC97H and MHCC97L, which have exactly the same genetic background but with different invasion potentials. Meanwhile, the prognostic potential of three verified LncRNAs at cell line level was further validated in 59 HCC samples. Therefore, our results demonstrated that the aberrant expression of LncRNAs might be responsible for the HCC invasion and metastasis and provide fundamental information for further study the LncRNAs involved molecular mechanisms of the invasion and metastasis of HCC.
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Literature
1.
go back to reference Jemal A et al. Global cancer statistics. CA: Cancer J Clin. 2011;2:69–90. Jemal A et al. Global cancer statistics. CA: Cancer J Clin. 2011;2:69–90.
2.
go back to reference Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA: Cancer J Clin. 2012;1:10–29. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA: Cancer J Clin. 2012;1:10–29.
4.
go back to reference Rahbari NN, Mehrabi A, Mollberg NM, Müller SA, Koch M, Büchler MW, et al. Hepatocellular carcinoma: current management and perspectives for the future. Ann Surg. 2011;3:453–69.CrossRef Rahbari NN, Mehrabi A, Mollberg NM, Müller SA, Koch M, Büchler MW, et al. Hepatocellular carcinoma: current management and perspectives for the future. Ann Surg. 2011;3:453–69.CrossRef
5.
go back to reference Ng KM, Yan T, Black D, Chu FC, Morris DL. Prognostic determinants for survival after resection/ablation of a large hepatocellular carcinoma. HPB (Oxford). 2009;4:311–20.CrossRef Ng KM, Yan T, Black D, Chu FC, Morris DL. Prognostic determinants for survival after resection/ablation of a large hepatocellular carcinoma. HPB (Oxford). 2009;4:311–20.CrossRef
6.
go back to reference Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;6:904–14.CrossRef Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;6:904–14.CrossRef
7.
go back to reference Huang J-l, Zheng L, Hu Y-W. Characteristics of long noncoding RNA and its relation to hepatocellular carcinoma. Carcinogenesis. 2014;3:507–14.CrossRef Huang J-l, Zheng L, Hu Y-W. Characteristics of long noncoding RNA and its relation to hepatocellular carcinoma. Carcinogenesis. 2014;3:507–14.CrossRef
9.
go back to reference Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;4:629–41.CrossRef Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;4:629–41.CrossRef
10.
go back to reference Quagliata L et al. LncRNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Hepatology. 2013;3:911–23. Quagliata L et al. LncRNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Hepatology. 2013;3:911–23.
11.
go back to reference Panzitt K et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology. 2007;1:330–42.CrossRef Panzitt K et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology. 2007;1:330–42.CrossRef
12.
go back to reference Wang J et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 2010;16:5366–83.CrossRef Wang J et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 2010;16:5366–83.CrossRef
13.
go back to reference Yang F et al. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology. 2011;5:1679–89.CrossRef Yang F et al. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology. 2011;5:1679–89.CrossRef
14.
go back to reference Yuan J-H et al. A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;5:666–81.CrossRef Yuan J-H et al. A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;5:666–81.CrossRef
15.
go back to reference Wang F, Yuan J-H, Wang S-B, Yang F, Yuan S-X, Ye C, et al. Oncofetal long noncoding RNA PVT1 promotes proliferation and stem cell-like property of hepatocellular carcinoma cells by stabilizing NOP2. Hepatology. 2014;4:1278–90.CrossRef Wang F, Yuan J-H, Wang S-B, Yang F, Yuan S-X, Ye C, et al. Oncofetal long noncoding RNA PVT1 promotes proliferation and stem cell-like property of hepatocellular carcinoma cells by stabilizing NOP2. Hepatology. 2014;4:1278–90.CrossRef
16.
go back to reference Yu W et al. Tumor suppressor long non-coding RNA, MT1DP is negatively regulated by YAP and Runx2 to inhibit FoxA1 in liver cancer cells. Cell Signal. 2014;12:2961–8.CrossRef Yu W et al. Tumor suppressor long non-coding RNA, MT1DP is negatively regulated by YAP and Runx2 to inhibit FoxA1 in liver cancer cells. Cell Signal. 2014;12:2961–8.CrossRef
17.
go back to reference Ørom UA et al. Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010;1:46–58.CrossRef Ørom UA et al. Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010;1:46–58.CrossRef
18.
go back to reference Barabási A-L, Oltvai ZN. Network biology: understanding the cell’s functional organization. Nat Rev Genet. 2004;2:101–13.CrossRef Barabási A-L, Oltvai ZN. Network biology: understanding the cell’s functional organization. Nat Rev Genet. 2004;2:101–13.CrossRef
19.
go back to reference Dinger ME et al. Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res. 2008;9:1433–45.CrossRef Dinger ME et al. Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res. 2008;9:1433–45.CrossRef
21.
go back to reference Carninci P et al. The transcriptional landscape of the mammalian genome. Science. 2005;5740:1559–63. Carninci P et al. The transcriptional landscape of the mammalian genome. Science. 2005;5740:1559–63.
22.
go back to reference Wang X et al. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature. 2008;7200:126–30.CrossRef Wang X et al. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature. 2008;7200:126–30.CrossRef
23.
go back to reference Faghihi MA, Wahlestedt C. Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol. 2009;9:637–43.CrossRef Faghihi MA, Wahlestedt C. Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol. 2009;9:637–43.CrossRef
24.
go back to reference Louro R et al. Conserved tissue expression signatures of intronic noncoding RNAs transcribed from human and mouse loci. Genomics. 2008;1:18–25.CrossRef Louro R et al. Conserved tissue expression signatures of intronic noncoding RNAs transcribed from human and mouse loci. Genomics. 2008;1:18–25.CrossRef
25.
go back to reference Louro R, Smirnova AS, Verjovski-Almeida S. Long intronic noncoding RNA transcription: expression noise or expression choice? Genomics. 2009;4:291–8.CrossRef Louro R, Smirnova AS, Verjovski-Almeida S. Long intronic noncoding RNA transcription: expression noise or expression choice? Genomics. 2009;4:291–8.CrossRef
26.
go back to reference Trinklein ND et al. An abundance of bidirectional promoters in the human genome. Genome Res. 2004;1:62–6. Trinklein ND et al. An abundance of bidirectional promoters in the human genome. Genome Res. 2004;1:62–6.
27.
go back to reference Morris KV et al. Bidirectional transcription directs both transcriptional gene activation and suppression in human cells. PLoS Genet. 2008;11:e1000258.CrossRef Morris KV et al. Bidirectional transcription directs both transcriptional gene activation and suppression in human cells. PLoS Genet. 2008;11:e1000258.CrossRef
28.
go back to reference Liu J et al. Genome-wide analysis uncovers regulation of long intergenic noncoding RNAs in Arabidopsis. Plant Cell Online. 2012;11:4333–45.CrossRef Liu J et al. Genome-wide analysis uncovers regulation of long intergenic noncoding RNAs in Arabidopsis. Plant Cell Online. 2012;11:4333–45.CrossRef
29.
go back to reference Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;6:703–19.CrossRef Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;6:703–19.CrossRef
30.
go back to reference Prensner JR et al. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol. 2011;8:742–9.CrossRef Prensner JR et al. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol. 2011;8:742–9.CrossRef
31.
go back to reference Gupta RA et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;7291:1071–6.CrossRef Gupta RA et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;7291:1071–6.CrossRef
32.
go back to reference Gutschner T, Hämmerle M, Diederichs S. MALAT1—a paradigm for long noncoding RNA function in cancer. J Mol Med. 2013;7:791–801.CrossRef Gutschner T, Hämmerle M, Diederichs S. MALAT1—a paradigm for long noncoding RNA function in cancer. J Mol Med. 2013;7:791–801.CrossRef
33.
go back to reference Braconi C et al. Expression and functional role of a transcribed noncoding RNA with an ultraconserved element in hepatocellular carcinoma. Proc Natl Acad Sci. 2011;2:786–91.CrossRef Braconi C et al. Expression and functional role of a transcribed noncoding RNA with an ultraconserved element in hepatocellular carcinoma. Proc Natl Acad Sci. 2011;2:786–91.CrossRef
34.
go back to reference Huang JF et al. Hepatitis B virus X protein (HBx)-related long noncoding RNA (LncRNA) down-regulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin. Hepatology. 2013;5:1882–92.CrossRef Huang JF et al. Hepatitis B virus X protein (HBx)-related long noncoding RNA (LncRNA) down-regulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin. Hepatology. 2013;5:1882–92.CrossRef
35.
go back to reference Yang F et al. Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell. 2013;6:1083–96.CrossRef Yang F et al. Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell. 2013;6:1083–96.CrossRef
36.
go back to reference Tsang WP, Kwok T. Riboregulator H19 induction of MDR1-associated drug resistance in human hepatocellular carcinoma cells. Oncogene. 2007;33:4877–81.CrossRef Tsang WP, Kwok T. Riboregulator H19 induction of MDR1-associated drug resistance in human hepatocellular carcinoma cells. Oncogene. 2007;33:4877–81.CrossRef
37.
38.
go back to reference Kutter C et al. Rapid turnover of long noncoding RNAs and the evolution of gene expression. PLoS Genet. 2012;7:e1002841.CrossRef Kutter C et al. Rapid turnover of long noncoding RNAs and the evolution of gene expression. PLoS Genet. 2012;7:e1002841.CrossRef
39.
go back to reference Derrien T et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;9:1775–89.CrossRef Derrien T et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;9:1775–89.CrossRef
40.
go back to reference Liu L et al. Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3β/Snail signaling. Hepatology. 2013;2:531–43. Liu L et al. Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3β/Snail signaling. Hepatology. 2013;2:531–43.
41.
go back to reference Jiang D-K et al. Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. Nat Genet. 2012;1:72–5.CrossRef Jiang D-K et al. Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. Nat Genet. 2012;1:72–5.CrossRef
42.
go back to reference Jiang J-H et al. An X-chromosomal association study identifies a susceptibility locus at Xq22. 1 for hepatitis B virus-related hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 2013;6:586–95.CrossRef Jiang J-H et al. An X-chromosomal association study identifies a susceptibility locus at Xq22. 1 for hepatitis B virus-related hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 2013;6:586–95.CrossRef
43.
go back to reference Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;3:155–9.CrossRef Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;3:155–9.CrossRef
44.
go back to reference Sulzmaier FJ, Ramos JW. RSK isoforms in cancer cell invasion and metastasis. Cancer Res. 2013;20:6099–105.CrossRef Sulzmaier FJ, Ramos JW. RSK isoforms in cancer cell invasion and metastasis. Cancer Res. 2013;20:6099–105.CrossRef
Metadata
Title
Invasion and metastasis-related long noncoding RNA expression profiles in hepatocellular carcinoma
Authors
Yunzhen Gao
Geng Chen
Yongyi Zeng
Jinhua Zeng
Minjie Lin
Xiaolong Liu
Jingfeng Liu
Publication date
01-10-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 10/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3408-0

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