Advertisement

Tumor Biology

, Volume 37, Issue 10, pp 13091–13100 | Cite as

Transcriptome profiling of lncRNA and co-expression networks in esophageal squamous cell carcinoma by RNA sequencing

  • Yuan Li
  • Xuejiao Shi
  • Wenhui Yang
  • Zhiliang Lu
  • Pan Wang
  • Zhaoli Chen
  • Jie He
Original Article

Abstract

Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cancer. To identify novel targets for further study in esophageal squamous cell carcinoma (ESCC), we performed a genome-wide analysis of lncRNA expression in 12 ESCC tumor and normal tissues. Publicly available RNA-seq data were downloaded from the NCBI, GEO, and Co-LncRNA databases, and lncRNA and messenger RNA (mRNA) expression profiles were analyzed. In total, 127 lncRNAs were found to be differentially expressed, with a greater than fourfold change in ESCC tumor tissues compared with normal tissues. Among these lncRNAs, 98 were upregulated and 29 downregulated. Moreover, 1469 network nodes and 1720 connection edges between 119 lncRNAs and 1350 coding genes were integrated into the lncRNA and mRNA co-expression network. Bioinformatic analysis using GO terms revealed that these dysregulated lncRNAs are associated with developmental processes, proteinaceous extracellular matrix, and protein binding activity, with ECM-receptor interaction and the PI3K-Akt signaling pathway enrichment. Lastly, qRT-PCR results verified two significantly upregulated lncRNAs and three significantly downregulated lncRNAs in 50 pairs of ESCC tissues and adjacent normal tissues. These results reveal the landscape of ESCC-associated lncRNAs and co-expression networks, providing important insight regarding the lncRNAs involved in ESCC.

Keywords

Long non-coding RNA lncRNA Esophageal squamous cell carcinoma ESCC Co-expression network 

Notes

Compliance with ethical standards

Samples were obtained with informed consent, and the study was approved by the medical ethics committee of the National Cancer Center/Cancer Hospital.

Funding

The work was supported by National Natural Science Foundation of China (81301851, U1302223), The National Key Basic Research Development (973) Plan (2014CB542006) and PUMC Youth Fund (33320140169).

Supplementary material

13277_2016_5227_MOESM1_ESM.xlsx (22 kb)
ESM 1 (XLSX 21 kb)
13277_2016_5227_MOESM2_ESM.xlsx (278 kb)
ESM 2 (XLSX 278 kb)
13277_2016_5227_MOESM3_ESM.xlsx (127 kb)
ESM 3 (XLSX 127 kb)
13277_2016_5227_MOESM4_ESM.xlsx (35 kb)
ESM 4 (XLSX 35 kb)
13277_2016_5227_MOESM5_ESM.xlsx (39 kb)
ESM 5 (XLSX 39 kb)

References

  1. 1.
    Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet. 2013;381:400–12. doi: 10.1016/S0140-6736(12)60643-6.CrossRefPubMedGoogle Scholar
  2. 2.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108. doi: 10.3322/caac.21262.CrossRefPubMedGoogle Scholar
  3. 3.
    Okines A, Cunningham D, Chau I. Targeting the human EGFR family in esophagogastric cancer. Nat Rev Clin Oncol. 2011;8:492–503. doi: 10.1038/nrclinonc.2011.45.CrossRefPubMedGoogle Scholar
  4. 4.
    Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66. doi: 10.1146/annurev-biochem-051410-092902.CrossRefPubMedGoogle Scholar
  5. 5.
    Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38. doi: 10.1186/1476-4598-10-38.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Brunner AL, Beck AH, Edris B, Sweeney RT, Zhu SX, Li R, Montgomery K, Varma S, Gilks T, Guo X, Foley JW, Witten DM, Giacomini CP, Flynn RA, Pollack JR, Tibshirani R, Chang HY, van de Rijn M, West RB. Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers. Genome Biol. 2012;13:R75. doi: 10.1186/gb-2012-13-8-r75.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Guil S, Esteller M. Cis-acting noncoding RNAs: friends and foes. Nat Struct Mol Biol. 2012;19:1068–75. doi: 10.1038/nsmb.2428.CrossRefPubMedGoogle Scholar
  8. 8.
    Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15:7–21. doi: 10.1038/nrg3606.CrossRefPubMedGoogle Scholar
  9. 9.
    Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, RB W, van de Vijver MJ, Sukumar S, Chang HY. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6. doi: 10.1038/nature08975.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Liu B, Sun L, Liu Q, Gong C, Yao Y, Lv X, Lin L, Yao H, Su F, Li D, Zeng M, Song E. A cytoplasmic NF-kappaB interacting long noncoding RNA blocks IkappaB phosphorylation and suppresses breast cancer metastasis. Cancer Cell. 2015;27:370–81. doi: 10.1016/j.ccell.2015.02.004.CrossRefPubMedGoogle Scholar
  11. 11.
    Hu L, Wu Y, Tan D, Meng H, Wang K, Bai Y, Yang K. Up-regulation of long noncoding RNA MALAT1 contributes to proliferation and metastasis in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 2015;34:7. doi: 10.1186/s13046-015-0123-z.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Xu G, Chen J, Pan Q, Huang K, Pan J, Zhang W, Chen J, Yu F, Zhou T, Wang Y. Long noncoding RNA expression profiles of lung adenocarcinoma ascertained by microarray analysis. PLoS One. 2014;9:e104044. doi: 10.1371/journal.pone.0104044.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Shi Y, Liu Y, Wang J, Jie D, Yun T, Li W, Yan L, Wang K, Feng J. Downregulated long noncoding RNA BANCR promotes the proliferation of colorectal cancer cells via downregualtion of p21 expression. PLoS One. 2015;10:e0122679. doi: 10.1371/journal.pone.0122679.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Hirata H, Hinoda Y, Shahryari V, Deng G, Nakajima K, Tabatabai ZL, Ishii N, Dahiya R. Long noncoding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res. 2015;75:1322–31. doi: 10.1158/0008-5472.CAN-14-2931.CrossRefPubMedGoogle Scholar
  15. 15.
    Yang F, Huo XS, Yuan SX, Zhang L, Zhou WP, Wang F, Sun SH. Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell. 2013;49:1083–96. doi: 10.1016/j.molcel.2013.01.010.CrossRefPubMedGoogle Scholar
  16. 16.
    Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, Liu F, Pan W, Wang TT, Zhou CC, Wang SB, Wang YZ, Yang Y, Yang N, Zhou WP, Yang GS, Sun SH. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;25:666–81. doi: 10.1016/j.ccr.2014.03.010.CrossRefPubMedGoogle Scholar
  17. 17.
    Zhu J, Liu S, Ye F, Shen Y, Tie Y, Zhu J, Jin Y, Zheng X, Wu Y, Fu H. The long noncoding RNA expression profile of hepatocellular carcinoma identified by microarray analysis. PLoS One. 2014;9:e101707. doi: 10.1371/journal.pone.0101707.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Wu W, Bhagat TD, Yang X, Song JH, Cheng Y, Agarwal R, Abraham JM, Ibrahim S, Bartenstein M, Hussain Z, Suzuki M, Yu Y, Chen W, Eng C, Greally J, Verma A, Meltzer SJ. Hypomethylation of noncoding DNA regions and overexpression of the long noncoding RNA, AFAP1-AS1, in Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterology. 2013;144:956–66 e4. doi: 10.1053/j.gastro.2013.01.019.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Chen FJ, Sun M, Li SQ, QQ W, Ji L, Liu ZL, Zhou GZ, Cao G, Jin L, Xie HW, Wang CM, Lv J, De W, Wu M, Cao XF. Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis. Mol Carcinog. 2013;52:908–15. doi: 10.1002/mc.21944.CrossRefPubMedGoogle Scholar
  20. 20.
    Lv XB, Lian GY, Wang HR, Song E, Yao H, Wang MH. Long noncoding RNA HOTAIR is a prognostic marker for esophageal squamous cell carcinoma progression and survival. PLoS One. 2013;8:e63516. doi: 10.1371/journal.pone.0063516.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Chen D, Zhang Z, Mao C, Zhou Y, Yu L, Yin Y, Wu S, Mou X, Zhu Y. ANRIL inhibits p15(INK4b) through the TGFbeta1 signaling pathway in human esophageal squamous cell carcinoma. Cell Immunol. 2014;289:91–6. doi: 10.1016/j.cellimm.2014.03.015.CrossRefPubMedGoogle Scholar
  22. 22.
    Li JY, Ma X, Zhang CB. Overexpression of long non-coding RNA UCA1 predicts a poor prognosis in patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2014;7:7938–44.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Shi WH, QQ W, Li SQ, Yang TX, Liu ZH, Tong YS, Tuo L, Wang S, Cao XF. Upregulation of the long noncoding RNA PCAT-1 correlates with advanced clinical stage and poor prognosis in esophageal squamous carcinoma. Tumor Biol. 2015;36:2501–7. doi: 10.1007/s13277-014-2863-3.CrossRefGoogle Scholar
  24. 24.
    Yao W, Bai Y, Li Y, Guo L, Zeng P, Wang Y, Qi B, Liu S, Qin X, Li Y, Zhao B. Upregulation of MALAT-1 and its association with survival rate and the effect on cell cycle and migration in patients with esophageal squamous cell carcinoma. Tumour Biol. 2015:1–8. doi: 10.1007/s13277-015-4223-3.
  25. 25.
    Tong M, Chan KW, Bao JYJ, Wong KY, Chen JN, Kwan PS, Tang KH, Fu L, Qin YR, Lok S, Guan XY, Ma S. Rab25 is a tumor suppressor gene with antiangiogenic and anti-invasive activities in esophageal squamous cell carcinoma. Cancer Res. 2012;72:6024–35. doi: 10.1158/0008-5472.CAN-12-1269.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhao Z, Bai J, Wu A, Wang Y, Zhang J, Wang Z, Li Y, Xu J, Li X. Co-LncRNA: investigating the lncRNA combinatorial effects in GO annotations and KEGG pathways based on human RNA-seq data. Database (Oxford). 2015;2015:bav082. doi: 10.1093/database/bav082.Google Scholar
  27. 27.
    Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43:e47. doi: 10.1093/nar/gkv007.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Khachane AN, Harrison PM. Mining mammalian transcript data for functional long non-coding RNAs. PLoS One. 2010;5:e10316. doi: 10.1371/journal.pone.0010316.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Hung T, Chang HY. Long noncoding RNA in genome regulation prospects and mechanisms. RNA Biol. 2010;7:582–5.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ma MZ, Chu BF, Zhang Y, Weng MZ, Qin YY, Gong W, Quan ZW. Long non-coding RNA CCAT1 promotes gallbladder cancer development via negative modulation of miRNA-218-5p. Cell Death Dis. 2015;6:e1583. doi: 10.1038/cddis.2014.541.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Xiang JF, Yin QF, Chen T, Zhang Y, Zhang XO, Wu Z, Zhang S, Wang HB, Ge J, Lu X, Yang L, Chen LL. Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus. Cell Res. 2014;24:513–31. doi: 10.1038/cr.2014.35.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Deng L, Yang SB, FF X, Zhang JH. Long noncoding RNA CCAT1 promotes hepatocellular carcinoma progression by functioning as let-7 sponge. J Exp Clin Cancer Res. 2015;34:18. doi: 10.1186/s13046-015-0136-7.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Zhu HQ, Zhou X, Chang H, Li HG, Liu FF, Ma CQ, Lu J. Aberrant expression of CCAT1 regulated by c-Myc predicts the prognosis of hepatocellular carcinoma. Asian Pac J Cancer Prev. 2015;16:5181–5.CrossRefPubMedGoogle Scholar
  34. 34.
    Yang F, Xue X, Bi J, Zheng L, Zhi K, Gu Y, Fang G. Long noncoding RNA CCAT1, which could be activated by c-Myc, promotes the progression of gastric carcinoma. J Cancer Res Clin Oncol. 2013;139:437–45. doi: 10.1007/s00432-012-1324-x.CrossRefPubMedGoogle Scholar
  35. 35.
    Wang J, Qiu M, Xu Y, Li M, Dong G, Mao Q, Yin R, Xu L. Long noncoding RNA CCAT2 correlates with smoking in esophageal squamous cell carcinoma. Tumour Biol. 2015;36:5523–8. doi: 10.1007/s13277-015-3220-x.CrossRefPubMedGoogle Scholar
  36. 36.
    Loebel DAF, Tsoi B, Wong N, Tam PPL. A conserved noncoding intronic transcript at the mouse Dnm3 locus. Genomics. 2005;85:782–9. doi: 10.1016/j.ygeno.2005.02.001.CrossRefPubMedGoogle Scholar
  37. 37.
    Chen L, Chen R, Kemper S, Charrier A, Brigstock DR. Suppression of fibrogenic signaling in hepatic stellate cells by Twist1-dependent microRNA-214 expression: role of exosomes in horizontal transfer of Twist1. Am J Physiol Gastrointest Liver Physiol. 2015;309:G491–9. doi: 10.1152/ajpgi.00140.2015.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Lee YB, Bantounas I, Lee DY, Phylactou L, Caldwell MA, Uney JB. Twist-1 regulates the miR-199a/214 cluster during development. Nucleic Acids Res. 2009;37:123–8. doi: 10.1093/nar/gkn920.CrossRefPubMedGoogle Scholar
  39. 39.
    Qin Y, Buermans HP, van Kester MS, van der Fits L, Out-Luiting JJ, Osanto S, Willemze R, Vermeer MH, Tensen CP. Deep-sequencing analysis reveals that the miR-199a2/214 cluster within DNM3os represents the vast majority of aberrantly expressed microRNAs in Sezary syndrome. J Investig Dermatol. 2012;132:1520–2. doi: 10.1038/jid.2011.481.CrossRefPubMedGoogle Scholar
  40. 40.
    Pounds S, Morris SW. Estimating the occurrence of false positives and false negatives in microarray studies by approximating and partitioning the empirical distribution of p-values. Bioinformatics. 2003;19:1236–42.CrossRefPubMedGoogle Scholar
  41. 41.
    Wu J, Lenchik NI, Gerling IC. Approaches to reduce false positives and false negatives in the analysis of microarray data: applications in type 1 diabetes research. BMC Genomics. 2008;9(Suppl 2):S12. doi: 10.1186/1471-2164-9-S2-S12.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kim SH, Turnbull J, Guimond S. Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J Endocrinol. 2011;209:139–51. doi: 10.1530/JOE-10-0377.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Thoracic Surgery, National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.Department of Oncologythe First Hospital of Shanxi Medical UniversityTaiyuanChina

Personalised recommendations