Tumor Biology

, Volume 37, Issue 2, pp 1983–1993 | Cite as

Upregulated expression of long non-coding RNA LINC00982 regulates cell proliferation and its clinical relevance in patients with gastric cancer

  • Zheng-hua Fei
  • Xiao-juan Yu
  • Ming Zhou
  • Hua-fang Su
  • Zhen Zheng
  • Cong-ying Xie
Original Article


Emerging evidences indicate that dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be used as diagnosis and prognosis biomarker or potential therapeutic targets. Therefore, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. In this study, we identified a novel lncRNA LINC00982, whose expression was downregulated in tumor tissues in 106 patients with gastric cancer (GC) compared with those in the adjacent normal tissues (P < 0.001). Furthermore, decreased LINC00982 expression was negatively correlated with invasion depth (P < 0.001), advanced TNM stage (P = 0.004), and regional lymph node metastasis (P = 0.005). LINC00982 levels were robust in differentiating gastric cancer tissues from controls [area under the curve (AUC) = 0.742; 95 % confidence interval (CI) = 0.678–0.800, P < 0.01]. Kaplan–Meier analysis demonstrated that decreased LINC00982 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that LINC00982 could be an independent prognostic marker. The levels of LINC00982 in gastric juice from gastric patients were significantly lower than those from normal subjects (P = 0.026). Furthermore, knockdown of LINC00982 expression by small interfering RNA (siRNA) could promote cell proliferation and cell cycle progression, while ectopic expression of LINC00982 inhibited cell proliferation and rendered cell cycle arrest in GC cells partly via regulating P15 and P16 protein expressions. Our findings present that decreased lncRNA LINC00982 could be identified as a poor prognostic biomarker in GC and regulate cell proliferation.


Long non-coding RNA LINC00982 Gastric cancer Clinical relevance 


Conflicts of interest


Ethics approval and consent to participate

The study was approved by the Ethics Committee on Human Research of the First Affiliated Hospital of Wenzhou Medical University, Huai’an First People’s Hospital, and Yangzhou No.1 People’s Hospital, and written informed consent was obtained from all patients.

Supplementary material

13277_2015_3979_MOESM1_ESM.xls (16 kb)
Table S1 Primers used for qRT-PCR. (XLS 16 kb)


  1. 1.
    Moore MA, Attasara P, Khuhaprema T, Le TN, Nguyen TH, Raingsey PP, et al. Cancer epidemiology in mainland South-East Asia—past, present and future. Asian Pac J Cancer Prev. 2010;11 Suppl 2:67–80.PubMedGoogle Scholar
  2. 2.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.CrossRefPubMedGoogle Scholar
  3. 3.
    Sapari NS, Loh M, Vaithilingam A, Soong R. Clinical potential of DNA methylation in gastric cancer: a meta-analysis. PloS ONE. 2012;7.Google Scholar
  4. 4.
    Milne AN, Carneiro F, O'Morain C, Offerhaus GJA. Nature meets nurture: molecular genetics of gastric cancer. Hum Genet. 2009;126:615–28.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Muers M. RNA genome-wide views of long non-coding RNAs. Nat Rev Genet. 2011;12.Google Scholar
  6. 6.
    Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.CrossRefPubMedGoogle Scholar
  7. 7.
    Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007;129:1311–23.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Calin GA, Liu CG, Ferracin M, Hyslop T, Spizzo R, Sevignani C, et al. Ultraconserved regions encoding ncRNAs are, altered in human leukemias and carcinomas. Cancer Cell. 2007;12:215–29.CrossRefPubMedGoogle Scholar
  9. 9.
    Lin R, Maeda S, Liu C, Karin M, Edgington TS. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene. 2007;26:851–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Hirata H, Hinoda Y, Shahryari V, Deng GR, Nakajima K, Tabatabai ZL, et al. Long noncoding RNA MALAT1 promotes aggressive renal cell carcinoma through EZH2 and interacts with miR-205. Cancer Res. 2015;75:1322–31.CrossRefPubMedGoogle Scholar
  11. 11.
    Okugawa Y, Toiyama Y, Hur K, Toden S, Saigusa S, Tanaka K, et al. Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis. Carcinogenesis. 2014;35:2731–9.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Sun M, Jin FY, Xia R, Kong R, Li JH, Xu TP, et al. Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer. 2014;14.Google Scholar
  13. 13.
    Sun M, Xia R, Jin FY, Xu TP, Liu ZJ, De W, et al. Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer. Tumor Biology. 2014;35:1065–73.CrossRefPubMedGoogle Scholar
  14. 14.
    Kong R, Zhang EB, Yin DD, You LH, Xu TP, Chen WM, et al. Long noncoding RNA PVT1 indicates a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically regulating p15 and p16. Mol Cancer. 2015;14.Google Scholar
  15. 15.
    Qi P, Du X. The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol. 2013;26:155–65.CrossRefPubMedGoogle Scholar
  16. 16.
    Risueno A, Fontanillo C, Dinger ME, De Las RJ. GATExplorer: Genomic and transcriptomic explorer; mapping expression probes to gene loci, transcripts, exons and ncRNAs. Bmc Bioinformatics. 2010;11.Google Scholar
  17. 17.
    Pang KC, Stephen S, Dinger ME, Engstrom PG, Lenhard B, Mattick JS. RNAdb 2.0-an expanded database of mammalian non-coding RNAs. Nucleic Acids Res. 2007;35:D178–82.CrossRefPubMedGoogle Scholar
  18. 18.
    Du Z, Fei T, Verhaak RGW, Su Z, Zhang Y, Brown M, et al. Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer. Nat Struct Mol Biol. 2013;20:908.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Li Q, Su ZJ, Xu XY, Liu GF, Song XH, Wang RJ, et al. AS1DHRS4, a head-to-head natural antisense transcript, silences the DHRS4 gene cluster in cis and trans. Proc Natl Acad Sci U S A. 2012;109:14110–5.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, et al. Structure of the heterodimer of human nono and paraspeckle protein component 1 and analysis of its role in subnuclear body formation. Proc Natl Acad Sci U S A. 2012;109:4846–50.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Srikantan V, Zou Z, Petrovics G, Xu L, Augustus M, Davis L, et al. PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer. Proc Natl Acad Sci U S A. 2000;97:12216–21.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Prensner JR, Sahu A, Iyer MK, Malik R, Chandler B, Asangani IA, et al. The incRNAs PCGEM1 and PRNCR1 are not implicated in castration resistant prostate cancer. Oncotarget. 2014;5:1434–8.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Ji P, Diederichs S, Wang W, Boing S, Metzger R, Schneider PM, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22:8031–41.CrossRefPubMedGoogle Scholar
  24. 24.
    Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, et al. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 2013;32:1616–25.CrossRefPubMedGoogle Scholar
  25. 25.
    Xu TP, Huang MD, Xia R, Liu XX, Sun M, Yin L, et al. Decreased expression of the long non-coding RNA FENDRR is associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectin1 expression. J Hematol Oncol. 2014;7:63.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lim SH, Kaldis P. Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development. 2013;140:3079–93.Google Scholar
  27. 27.
    Matsumoto Y, Marusawa H, Kinoshita K, Niwa Y, Sakai Y, Chiba T. Up-regulation of activation-induced cytidine deaminase causes genetic aberrations at the CDKN2b-CDKN2a in gastric cancer. Gastroenterology. 2010;139:1984–94.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Zheng-hua Fei
    • 1
  • Xiao-juan Yu
    • 2
  • Ming Zhou
    • 3
  • Hua-fang Su
    • 1
  • Zhen Zheng
    • 1
  • Cong-ying Xie
    • 1
  1. 1.Radiotherapy and Chemotherapy DepartmentThe 1st Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
  2. 2.Department of Medical OncologyHuai’an First People’s HospitalJiangsuPeople’s Republic of China
  3. 3.Department of General SurgeryYangzhou No.1 People’s Hospital, The Second Clinical School of Yangzhou UniversityJiangsu ProvincePeople’s Republic of China

Personalised recommendations