Skip to main content

Advertisement

Log in

Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a long non-coding RNA (lncRNA), is up-regulated in many solid tumors and associated with cancer metastasis and recurrence. However, its role in hepatocellular carcinoma (HCC) remains poorly understood. In the present study, we evaluated the expression of MALAT1 by quantitative real-time PCR in 9 liver cancer cell lines and 112 HCC cases including 60 cases who received liver transplantation (LT) with complete follow-up data. Moreover, small interfering RNA (siRNA) was used to inhibit MALAT1 expression to investigate its biological role in tumor progression. We found that MALAT1 was up-regulated in both cell lines and clinical tissue samples. Patients with high expression level of MALAT1 had a significantly increased risk of tumor recurrence after LT, particularly in patients who exceeded the Milan criteria. On multivariate analysis, MALAT1 was an independent prognostic factor for predicting HCC recurrence (hazard ratio, 3.280, P = 0.003).In addition, inhibition of MALAT1 in HepG2 cells could effectively reduce cell viability, motility, invasiveness, and increase the sensitivity to apoptosis. Our data suggest that lncRNA MALAT1 play an important role in tumor progression and could be a novel biomarker for predicting tumor recurrence after LT and serve as a promising therapeutic target.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

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

    Article  PubMed  CAS  Google Scholar 

  2. Okuda K. Hepatocellular carcinoma. J Hepatol. 2000;32:225–7.

    Article  PubMed  CAS  Google Scholar 

  3. Belghiti J, Kianmanesh R. Surgical treatment of hepatocellular carcinoma. HPB (Oxford). 2005;7:42–9.

    Article  Google Scholar 

  4. Bai DS, Dai Z, Zhou J, et al. Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma. Hepatology. 2009;49:460–70.

    Article  PubMed  CAS  Google Scholar 

  5. Sieghart W, Wang X, Schmid K, et al. Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria. J Hepatol. 2011;54:89–97.

    Article  PubMed  CAS  Google Scholar 

  6. Yang Y, Nagano H, Ota H, et al. Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection. Surgery. 2007;141:196–202.

    Article  PubMed  Google Scholar 

  7. Zheng SS, Xu X, Wu J, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85:1726–32.

    Article  PubMed  CAS  Google Scholar 

  8. Ørom UA, Derrien T, Beringer M, et al. Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010;143:46–58.

    Article  PubMed  Google Scholar 

  9. Chen LL, Gordon G. Long noncoding RNAs in mammalian cells: what, where, and why. WIREs RNA. 2010;1:2–21.

    PubMed  CAS  Google Scholar 

  10. Guo F, Li Y, Liu Y, Wang J, Li Y, Li G. Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. Acta Biochim Biophys Sin (Shanghai). 2010;42:224–9.

    Article  CAS  Google Scholar 

  11. Gupta RA, Shah N, Wang KC, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.

    Article  PubMed  CAS  Google Scholar 

  12. Ji P, Diederichs S, Wang W, 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.

    Article  PubMed  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. Luo JH, Ren B, Keryanov S, et al. Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas. Hepatology. 2006;44:1012–24.

    Article  PubMed  CAS  Google Scholar 

  15. Yamada K, Kano J, Tsunoda H, Yoshikawa H, Okubo C, Ishiyama T, Noguchi M. Phenotypic characterization of endometrial stromal sarcoma of the uterus. Cancer Sci. 2006;97:106–12.

    Article  PubMed  CAS  Google Scholar 

  16. Bioulac-Sage P, Rebouissou S, Sa Cunha A, et al. Clinical, morphologic, and molecular features defining so-called telangiectatic focal nodular hyperplasias of the liver. Gastroenterology. 2005;128:1211–8.

    Article  PubMed  Google Scholar 

  17. Feng YX, Zhao JS, Li JJ, et al. Liver cancer EphrinA2 promotes tumorigenicity through Rac1 Akt NF-kappaB signaling pathway 120. Hepatology. 2010;51:535–44.

    Article  PubMed  CAS  Google Scholar 

  18. Huang G, Hu Z, Li M, Cui Y, Li Y, Guo L, Jiang W, Lu SH. ECRG2 inhibits cancer cell migration, invasion and metastasis through the downregulation of uPA/plasmin activity. Carcinogenesis. 2007;28:2274–81.

    Article  PubMed  CAS  Google Scholar 

  19. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.

    Article  PubMed  CAS  Google Scholar 

  20. Song HY, Liu YK, Feng JT, et al. Proteomic analysis on metastasis-associated proteins of human hepatocellular carcinoma tissues. J Cancer Res Clin Oncol. 2006;132:92–8.

    Article  PubMed  CAS  Google Scholar 

  21. Grasso A, Stigliano R, Morisco F, et al. Liver transplantation and recurrent hepatocellular carcinoma: predictive value of nodule size in a retrospective and explant study. Transplantation. 2006;81:1532–41.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  23. Calin GA, Liu CG, Ferracin M, et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell. 2007;12:215–29.

    Article  PubMed  CAS  Google Scholar 

  24. Tsai MC, Spitale RC, Chang HY. Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res. 2011;7:3–7.

    Article  Google Scholar 

  25. Tseng JJ, Hsieh YT, Hsu SL, Chou MM. Metastasis associated lung adenocarcinoma transcript 1 is up-regulated in placenta previa increta/percreta and strongly associated with trophoblast-like cell invasion in vitro. Mol Hum Reprod. 2009;15:725–31.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the Major State Basic Research Development Program (NO.2009CB522407), the Major National S&T Program (NO. 2008ZX10002-026), and the Program for Innovative Research Team of Zhejiang Province of China (NO. 2009R50038) The authors would like to thank the surgeons and nurses for their valuable technical assistance and facilitating the collection of patient information.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shu-sen Zheng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lai, Mc., Yang, Z., Zhou, L. et al. Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol 29, 1810–1816 (2012). https://doi.org/10.1007/s12032-011-0004-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-011-0004-z

Keywords

Navigation