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Published in: Clinical & Experimental Metastasis 1-2/2018

01-02-2018 | Research Paper

Aberrant methylation-mediated silencing of lncRNA CTC-276P9.1 is associated with malignant progression of esophageal squamous cell carcinoma

Authors: Wei Guo, Shengnan Liu, Zhiming Dong, Yanli Guo, Chunyan Ding, Supeng Shen, Jia Liang, Baoen Shan

Published in: Clinical & Experimental Metastasis | Issue 1-2/2018

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Abstract

Downregulation and aberrant hypermethylation of long non-coding RNA CTC-276P9.1 have been detected in limited tumors. However, the distribution of methylated CpG sites and biological role of CTC-276P9.1 in esophageal squamous cell carcinoma (ESCC) progression and prognosis have not been fully clarified. The present study was to investigate the expression status and the distribution of methylated CpG sites within the three CpG islands of CTC-276P9.1, further to clarify its functional role and prognostic value in ESCC development and prognosis. Significant downregulation of CTC-276P9.1 was detected in esophageal cancer cells and ESCC tissues, and the expression of CTC-276P9.1 in ESCC tissues was associated with TNM stage, pathological differentiation, lymph node metastasis, and distant metastasis or recurrence. The expression level of CTC-276P9.1 in esophageal cancer cells was significantly reversed by treatment with 5-Aza-dC and TSA. The aberrant hypermethylation of the regions around the transcription start site was more tumor specific and associated with the expression levels of CTC-276P9.1. Moreover, histone modification may also participate in the regulation of CTC-276P9.1. Furthermore, over-expression of CTC-276P9.1 inhibited esophageal cancer cells proliferation and invasion in vitro, decreased the expression of proliferative markers and inhibited esophageal cancer cells invasion probably by regulating EMT. In addition, the dysregulation and hypermethylation of the regions around the transcription start site of CTC-276P9.1 were associated with poorer ESCC patients’ survival. These findings suggest that CTC-276P9.1 may act as a tumor suppressor and may be employed as a new prognostic factor and therapeutic target for ESCC.
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Literature
1.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108CrossRefPubMed Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108CrossRefPubMed
2.
go back to reference Napier KJ, Scheerer M, Misra S (2014) Esophageal cancer: A review of epidemiology, pathogenesis, staging workup and treatment modalities. World J Gastrointest Oncol 6:112–120CrossRefPubMedPubMedCentral Napier KJ, Scheerer M, Misra S (2014) Esophageal cancer: A review of epidemiology, pathogenesis, staging workup and treatment modalities. World J Gastrointest Oncol 6:112–120CrossRefPubMedPubMedCentral
3.
go back to reference Shahbaz Sarwar CM, Luketich JD, Landreneau RJ, Abbas G (2010) Esophageal cancer: an update. Int J Surg 8:417–422CrossRefPubMed Shahbaz Sarwar CM, Luketich JD, Landreneau RJ, Abbas G (2010) Esophageal cancer: an update. Int J Surg 8:417–422CrossRefPubMed
4.
go back to reference Guohong Z, Min S, Duenmei W, Songnian H, Min L, Jinsong L, Hongbin L, Feng Z, Dongping T, Heling Y, Zhicai L, Shiyong L, Quansheng G, Xiaoyun L, Yuxia G (2010) Genetic heterogeneity of oesophageal cancer in high-incidence areas of southern and northern China. PLoS ONE 5:e9668CrossRefPubMedPubMedCentral Guohong Z, Min S, Duenmei W, Songnian H, Min L, Jinsong L, Hongbin L, Feng Z, Dongping T, Heling Y, Zhicai L, Shiyong L, Quansheng G, Xiaoyun L, Yuxia G (2010) Genetic heterogeneity of oesophageal cancer in high-incidence areas of southern and northern China. PLoS ONE 5:e9668CrossRefPubMedPubMedCentral
5.
go back to reference Messmann H (2001) Squamous cell cancer of the oesophagus. Best Pract Res Clin Gastroenterol 15:249–265CrossRefPubMed Messmann H (2001) Squamous cell cancer of the oesophagus. Best Pract Res Clin Gastroenterol 15:249–265CrossRefPubMed
6.
go back to reference Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484–1488CrossRefPubMed Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484–1488CrossRefPubMed
7.
go back to reference Sun M, Kraus WL (2015) From discovery to function: the expanding roles of long noncoding RNAs in physiology and disease. Endocr Rev 36:25–64CrossRefPubMed Sun M, Kraus WL (2015) From discovery to function: the expanding roles of long noncoding RNAs in physiology and disease. Endocr Rev 36:25–64CrossRefPubMed
8.
go back to reference Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS (2010) Non-coding RNAs: regulators of disease. J Pathol 220:126–139CrossRefPubMed Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS (2010) Non-coding RNAs: regulators of disease. J Pathol 220:126–139CrossRefPubMed
9.
go back to reference Lipovich L, Johnson R, Lin CY (2010) MacroRNA underdogs in a microRNA world: evolutionary, regulatory, and biomedical significance of mammalian long non-protein-coding RNA. Biochim Biophys Acta 1799:597–615CrossRefPubMed Lipovich L, Johnson R, Lin CY (2010) MacroRNA underdogs in a microRNA world: evolutionary, regulatory, and biomedical significance of mammalian long non-protein-coding RNA. Biochim Biophys Acta 1799:597–615CrossRefPubMed
11.
go back to reference Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227CrossRefPubMedPubMedCentral Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227CrossRefPubMedPubMedCentral
12.
go back to reference Beckedorff FC, Amaral MS, Deocesano-Pereira C, Verjovski-Almeida S (2013) Long non-coding RNAs and their implications in cancer epigenetics. Biosci Rep 33 pii:e00061CrossRefPubMedPubMedCentral Beckedorff FC, Amaral MS, Deocesano-Pereira C, Verjovski-Almeida S (2013) Long non-coding RNAs and their implications in cancer epigenetics. Biosci Rep 33 pii:e00061CrossRefPubMedPubMedCentral
13.
go back to reference Dong Z, Zhang A, Liu S, Lu F, Guo Y, Zhang G, Xu F, Shi Y, Shen S, Liang J, Guo W (2017) Aberrant Methylation-mediated Silencing of lncRNA MEG3 Functions as a ceRNA in Esophageal Cancer. Mol Cancer Res 15:800–810CrossRefPubMed Dong Z, Zhang A, Liu S, Lu F, Guo Y, Zhang G, Xu F, Shi Y, Shen S, Liang J, Guo W (2017) Aberrant Methylation-mediated Silencing of lncRNA MEG3 Functions as a ceRNA in Esophageal Cancer. Mol Cancer Res 15:800–810CrossRefPubMed
14.
go back to reference Vrba L, Garbe JC, Stampfer MR, Futscher BW (2015) A lincRNA connected to cell mortality and epigenetically-silenced in most common human cancers. Epigenetics 10:1074–1083CrossRefPubMedPubMedCentral Vrba L, Garbe JC, Stampfer MR, Futscher BW (2015) A lincRNA connected to cell mortality and epigenetically-silenced in most common human cancers. Epigenetics 10:1074–1083CrossRefPubMedPubMedCentral
15.
go back to reference Liao M, Li B, Zhang S, Liu Q, Liao W, Xie W, Zhang Y (2017) Relationship between LINC00341 expression and cancer prognosis. Oncotarget 8:15283–15293PubMedPubMedCentral Liao M, Li B, Zhang S, Liu Q, Liao W, Xie W, Zhang Y (2017) Relationship between LINC00341 expression and cancer prognosis. Oncotarget 8:15283–15293PubMedPubMedCentral
16.
go back to reference Zhu YP, Bian XJ, Ye DW, Yao XD, Zhang SL, Dai B, Zhang HL, Shen YJ (2014) Long noncoding RNA expression signatures of bladder cancer revealed by microarray. Oncol Lett 7:1197–1202CrossRefPubMedPubMedCentral Zhu YP, Bian XJ, Ye DW, Yao XD, Zhang SL, Dai B, Zhang HL, Shen YJ (2014) Long noncoding RNA expression signatures of bladder cancer revealed by microarray. Oncol Lett 7:1197–1202CrossRefPubMedPubMedCentral
17.
go back to reference Yu G, Li C, Xie W, Wang Z, Gao H, Cao L, Hao L, Zhang Y (2017) Long non-coding RNA C5orf66-AS1 is downregulated in pituitary null cell adenomas and is associated with their invasiveness. Oncol Rep 38:1140–1148CrossRefPubMed Yu G, Li C, Xie W, Wang Z, Gao H, Cao L, Hao L, Zhang Y (2017) Long non-coding RNA C5orf66-AS1 is downregulated in pituitary null cell adenomas and is associated with their invasiveness. Oncol Rep 38:1140–1148CrossRefPubMed
18.
go back to reference Feng L, Houck JR, Lohavanichbutr P, Chen C (2017) Transcriptome analysis reveals differentially expressed lncRNAs between oral squamous cell carcinoma and healthy oral mucosa. Oncotarget 8:31521–31531PubMedPubMedCentral Feng L, Houck JR, Lohavanichbutr P, Chen C (2017) Transcriptome analysis reveals differentially expressed lncRNAs between oral squamous cell carcinoma and healthy oral mucosa. Oncotarget 8:31521–31531PubMedPubMedCentral
19.
go back to reference Zhi H, Ning S, Li X, Li Y, Wu W, Li X (2014) A novel reannotation strategy for dissecting DNA methylation patterns of human long intergenic non-coding RNAs in cancers. Nucleic Acids Res 42:8258–8270CrossRefPubMedPubMedCentral Zhi H, Ning S, Li X, Li Y, Wu W, Li X (2014) A novel reannotation strategy for dissecting DNA methylation patterns of human long intergenic non-coding RNAs in cancers. Nucleic Acids Res 42:8258–8270CrossRefPubMedPubMedCentral
20.
go back to reference Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408CrossRefPubMed Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408CrossRefPubMed
21.
go back to reference Sasaki M, Anast J, Bassett W, Kawakami T, Sakuragi N, Dahiya R (2003) Bisulfite conversion-specific and methylation-specific PCR: a sensitive technique for accurate evaluation of CpG methylation. Biochem Biophys Res Commun 309:305–309CrossRefPubMed Sasaki M, Anast J, Bassett W, Kawakami T, Sakuragi N, Dahiya R (2003) Bisulfite conversion-specific and methylation-specific PCR: a sensitive technique for accurate evaluation of CpG methylation. Biochem Biophys Res Commun 309:305–309CrossRefPubMed
22.
go back to reference Yu L, Liu C, Vandeusen J, Becknell B, Dai Z, Wu YZ, Raval A, Liu TH, Ding W, Mao C, Liu S, Smith LT, Lee S, Rassenti L, Marcucci G, Byrd J, Caligiuri MA, Plass C (2005) Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia. Nat Genet 37:265–274CrossRefPubMed Yu L, Liu C, Vandeusen J, Becknell B, Dai Z, Wu YZ, Raval A, Liu TH, Ding W, Mao C, Liu S, Smith LT, Lee S, Rassenti L, Marcucci G, Byrd J, Caligiuri MA, Plass C (2005) Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia. Nat Genet 37:265–274CrossRefPubMed
23.
go back to reference Wei G, Luo H, Sun Y, Li J, Tian L, Liu W, Liu L, Luo J, He J, Chen R (2015) Transcriptome profiling of esophageal squamous cell carcinoma reveals a long noncoding RNA acting as a tumor suppressor. Oncotarget 6:17065–17080PubMedPubMedCentral Wei G, Luo H, Sun Y, Li J, Tian L, Liu W, Liu L, Luo J, He J, Chen R (2015) Transcriptome profiling of esophageal squamous cell carcinoma reveals a long noncoding RNA acting as a tumor suppressor. Oncotarget 6:17065–17080PubMedPubMedCentral
24.
25.
go back to reference Ma X, Yu L, Wang P, Yang X (2017) Discovering DNA methylation patterns for long non-coding RNAs associated with cancer subtypes. Comput Biol Chem 69:164–170CrossRefPubMed Ma X, Yu L, Wang P, Yang X (2017) Discovering DNA methylation patterns for long non-coding RNAs associated with cancer subtypes. Comput Biol Chem 69:164–170CrossRefPubMed
26.
go back to reference Endoh M, Tamura G, Honda T, Homma N, Terashima M, Nishizuka S, Motoyama T (2005) RASSF2, a potential tumour suppressor, is silenced by CpG island hypermethylation in gastric cancer. Br J Cancer 93:1395–1399CrossRefPubMedPubMedCentral Endoh M, Tamura G, Honda T, Homma N, Terashima M, Nishizuka S, Motoyama T (2005) RASSF2, a potential tumour suppressor, is silenced by CpG island hypermethylation in gastric cancer. Br J Cancer 93:1395–1399CrossRefPubMedPubMedCentral
27.
go back to reference Homma N, Tamura G, Honda T, Matsumoto Y, Nishizuka S, Kawata S, Motoyama T (2006) Spreading of methylation within RUNX3 CpG island in gastric cancer. Cancer Sci 97:51–56CrossRefPubMed Homma N, Tamura G, Honda T, Matsumoto Y, Nishizuka S, Kawata S, Motoyama T (2006) Spreading of methylation within RUNX3 CpG island in gastric cancer. Cancer Sci 97:51–56CrossRefPubMed
29.
go back to reference Wang Y, Chen T, Huang H, Jiang Y, Yang L, Lin Z, He H, Liu T, Wu B, Chen J, Kamp DW, Liu G (2017) miR-363-3p inhibits tumor growth by targeting PCNA in lung adenocarcinoma. Oncotarget 8:20133–20144PubMedPubMedCentral Wang Y, Chen T, Huang H, Jiang Y, Yang L, Lin Z, He H, Liu T, Wu B, Chen J, Kamp DW, Liu G (2017) miR-363-3p inhibits tumor growth by targeting PCNA in lung adenocarcinoma. Oncotarget 8:20133–20144PubMedPubMedCentral
30.
go back to reference Karimian H, Arya A, Fadaeinasab M, Razavi M, Hajrezaei M, Karim Khan A, Mohd Ali H, Abdulla MA, Noordin MI (2017) Kelussia odoratissima Mozaff. activates intrinsic pathway of apoptosis in breast cancer cells associated with S phase cell cycle arrest via involvement of p21/p27 in vitro and in vivo. Drug Des Dev Ther 11:337–350CrossRef Karimian H, Arya A, Fadaeinasab M, Razavi M, Hajrezaei M, Karim Khan A, Mohd Ali H, Abdulla MA, Noordin MI (2017) Kelussia odoratissima Mozaff. activates intrinsic pathway of apoptosis in breast cancer cells associated with S phase cell cycle arrest via involvement of p21/p27 in vitro and in vivo. Drug Des Dev Ther 11:337–350CrossRef
31.
go back to reference Wang SC (2014) PCNA: a silent housekeeper or a potential therapeutic target? Trends Pharmacol Sci 35:178–186CrossRefPubMed Wang SC (2014) PCNA: a silent housekeeper or a potential therapeutic target? Trends Pharmacol Sci 35:178–186CrossRefPubMed
32.
go back to reference Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890CrossRefPubMed Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890CrossRefPubMed
Metadata
Title
Aberrant methylation-mediated silencing of lncRNA CTC-276P9.1 is associated with malignant progression of esophageal squamous cell carcinoma
Authors
Wei Guo
Shengnan Liu
Zhiming Dong
Yanli Guo
Chunyan Ding
Supeng Shen
Jia Liang
Baoen Shan
Publication date
01-02-2018
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 1-2/2018
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-018-9881-2

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