Skip to main content

Advertisement

Log in

Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Long non-coding RNAs (lncRNAs) have been demonstrated to be a critical role in cancer progression and prognosis. However, little is known about the pathological role of lncRNA HOXA transcript at the distal tip (HOTTIP) in tongue squamous cell carcinoma (TSCC) patients. The aim of this study is to measure the expression of lncRNA HOTTIP in TSCC patients and to explore the clinical significance of the lncRNA HOTTIP. The expression of lncRNA HOTTIP was measured in 86 TSCC tissues and 14 adjacent non-malignant tissues using qRT-PCR. In our study, results indicated that lncRNA HOTTIP was highly expressed in TSCC compared with adjacent non-malignant tissues (P < 0.001) and positively correlated with T stage (T1–2 vs. T3–4, P = 0.023), clinical stage (I–II stages vs. III–IV stages, P = 0.018), and distant metastasis (absent vs. present, P = 0.031) in TSCC patients. Furthermore, we also found that lncRNA HOTTIP overexpression was an unfavorable prognostic factor in TSCC patients (P < 0.001), regardless of T stage, distant metastasis, and clinical stage. Finally, overexpression of lncRNA HOTTIP was supposed to be an independent poor prognostic factor for TSCC patients through multivariate analysis (P = 0.023). In conclusion, increased lncRNA HOTTIP expression may be serve as an unfavorable prognosis predictor for TSCC patients. Nevertheless, further investigation with a larger sample size is needed to support our results.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.

    Article  PubMed  Google Scholar 

  2. Cannon TL, Lai DW, Hirsch D, Delacure M, Downey A, Kerr AR, et al. Squamous cell carcinoma of the oral cavity in nonsmoking women: a new and unusual complication of chemotherapy for recurrent ovarian cancer? Oncologist. 2012;17:1541–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dibble EH, Alvarez AC, Truong MT, Mercier G, Cook EF, Subramaniam RM. 18F-FDG metabolic tumor volume and total glycolytic activity of oral cavity and oropharyngeal squamous cell cancer: adding value to clinical staging. J Nuclear Med Off Publ Soc Nuclear Med. 2012;53:709–15.

    CAS  Google Scholar 

  4. Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;9:703–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Saxena A, Carninci P. Long non-coding RNA modifies chromatin: epigenetic silencing by long non-coding RNAs. BioEssays News Rev Mol Cell Dev Biol. 2011;33:830–9.

    Article  CAS  Google Scholar 

  7. Mattick JS, Makunin IV. Non-coding RNA. Hum Mol Genet. 2006;15(Spec No 1):R17–29.

    Article  CAS  PubMed  Google Scholar 

  8. Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.

    Article  CAS  PubMed  Google Scholar 

  9. Tano K, Mizuno R, Okada T, Rakwal R, Shibato J, Masuo Y, et al. Malat-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett. 2010;584:4575–80.

    Article  CAS  PubMed  Google Scholar 

  10. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43:904–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, et al. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011;472:120–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Quagliata L, Matter MS, Piscuoglio S, Arabi L, Ruiz C, Procino A, et al. Long noncoding RNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Hepatology. 2014;59:911–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jiang YJ, Bikle DD. LncRNA profiling reveals new mechanism for VDR protection against skin cancer formation. J Steroid Biochem Mol Biol. 2014;144(Pt A):87–90.

    CAS  PubMed  Google Scholar 

  14. Motoyama K, Inoue H, Nakamura Y, Uetake H, Sugihara K, Mori M. Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res Off J Am Assoc Cancer Res. 2008;14:2334–40.

    Article  CAS  Google Scholar 

  15. Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9.

    Article  CAS  PubMed  Google Scholar 

  16. Nie L, Wu HJ, Hsu JM, Chang SS, Labaff AM, Li CW, et al. Long non-coding RNAs: versatile master regulators of gene expression and crucial players in cancer. Am J Transl Res. 2012;4:127–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Eddy SR. Non-coding RNA genes and the modern RNA world. Nat Rev Genet. 2001;2:919–29.

    Article  CAS  PubMed  Google Scholar 

  18. Kung JT, Colognori D, Lee JT. Long noncoding RNAs: past, present, and future. Genetics. 2013;193:651–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21:354–61.

    Article  CAS  PubMed  Google Scholar 

  20. Hajjari M, Khoshnevisan A, Shin YK. Long non-coding RNAs in hematologic malignancies: road to translational research. Front Genet. 2013;4:250.

    PubMed  PubMed Central  Google Scholar 

  21. Iglesias-Linares A, Yanez-Vico RM, Gonzalez-Moles MA. Potential role of HDAC inhibitors in cancer therapy: insights into oral squamous cell carcinoma. Oral Oncol. 2010;46:323–9.

    Article  CAS  PubMed  Google Scholar 

  22. Perez-Sayans M, Somoza-Martin JM, Barros-Angueira F, Reboiras-Lopez MD, Gandara Rey JM, Garcia-Garcia A. Genetic and molecular alterations associated with oral squamous cell cancer (review). Oncol Rep. 2009;22:1277–82.

    Article  CAS  PubMed  Google Scholar 

  23. Gibb EA, Enfield KS, Stewart GL, Lonergan KM, Chari R, Ng RT, et al. Long non-coding RNAs are expressed in oral mucosa and altered in oral premalignant lesions. Oral Oncol. 2011;47:1055–61.

    Article  CAS  PubMed  Google Scholar 

  24. Fang Z, Wu L, Wang L, Yang Y, Meng Y, Yang H. Increased expression of the long non-coding RNA UCA1 in tongue squamous cell carcinomas: a possible correlation with cancer metastasis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117:89–95.

    Article  PubMed  Google Scholar 

  25. Gao W, Chan JY, Wong TS. Long non-coding RNA deregulation in tongue squamous cell carcinoma. BioMed Res Int. 2014;2014:405860.

    PubMed  PubMed Central  Google Scholar 

  26. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tsang FH, Au SL, Wei L, Fan DN, Lee JM, Wong CC, et al. Long non-coding RNA HOTTIP is frequently up-regulated in hepatocellular carcinoma and is targeted by tumour suppressive miR-125b. Liver Int Off J Int Assoc Study Liver. 2015;35:1597–606.

    CAS  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lei Zhao.

Additional information

Hua Zhang and Lei Zhao contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, H., Zhao, L., Wang, YX. et al. Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma. Tumor Biol. 36, 8805–8809 (2015). https://doi.org/10.1007/s13277-015-3645-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-3645-2

Keywords

Navigation