Clinical & Experimental Metastasis

, Volume 30, Issue 5, pp 651–658 | Cite as

Decreased expression of miR-126 correlates with metastatic recurrence of hepatocellular carcinoma

  • Hongyuan Chen
  • Ruizheng Miao
  • Junwei Fan
  • Zhongbo Han
  • Junyi Wu
  • Guoqiang Qiu
  • Huamei Tang
  • Zhihai PengEmail author
Research Paper


The liver transplant (LT) situation represents an attractive model for studying hepatocellular carcinoma (HCC) metastasis. Based on microarray data, we previously found that miR-126 expression was lower in tumor tissues of patients with post-LT HCC recurrence compared with non-recurrence. In this study, we examined the expression of miR-126 in HCC samples from 68 patients who had undergone LT using quantitative real-time PCR and analyzed its correlation with clinicopathological features and prognosis of patients. Furthermore, we performed experimental analyses to explore the involvement of miR-126 in HCC metastasis. We found that miR-126 levels were lower in tumor tissues of patients with post-LT HCC recurrence in comparison to patients with no-recurrence (p = 0.009). Lower expression of miR-126 in HCC was associated significantly with tumor recurrence (p = 0.011) and poor survival (p = 0.009) of patients. Functional studies indicated that ectopic expression of miR-126 significantly inhibits HCC cells migration, invasion, proliferation and colony formation in vitro, and suppresses experimental lung colonization in vivo. Our study revealed that down-regulation of miR-126 plays an important role in HCC metastasis, and suggest a potential application of miR-126 in prognosis prediction and HCC treatment.


miR-126 Hepatocellular carcinoma Liver transplantation Metastasis 



Hepatocellular carcinoma


Liver transplant




Quantitative real time-polymerase chain reaction


Formalin-fixed paraffin embedded


Mesenchymal epithelial transition


Overall survival



This study was supported by National Key Technology R&D Program (2008BAI60B03).

Conflict of interest

The authors disclosed no commercial or financial interest in the subject of study.


  1. 1.
    El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132(7):2557–2576PubMedCrossRefGoogle Scholar
  2. 2.
    Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108PubMedCrossRefGoogle Scholar
  3. 3.
    Thomas (2010) Hepatocellular carcinoma: consensus recommendations of the national cancer institute clinical trials planning meeting (vol 28, pg 3994, 2010). J Clin Oncol 28(36):5350–5550Google Scholar
  4. 4.
    Hanahan D (2000) The hallmarks of cancer. Cell 100(1):57–70PubMedCrossRefGoogle Scholar
  5. 5.
    White NMA, Fatoohi E, Metias M, Jung K, Stephan C, Yousef GM (2010) Metastamirs: a stepping stone towards improved cancer management. Nat Rev Clin Oncol 8(2):75–84PubMedCrossRefGoogle Scholar
  6. 6.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233PubMedCrossRefGoogle Scholar
  7. 7.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297PubMedCrossRefGoogle Scholar
  8. 8.
    Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355PubMedCrossRefGoogle Scholar
  9. 9.
    Ventura A, Jacks T (2009) MicroRNAs and cancer: short RNAs go a long way. Cell 136(4):586–591PubMedCrossRefGoogle Scholar
  10. 10.
    Iorio MV, Croce CM (2009) MicroRNAs in cancer: small molecules with a huge impact. J Clin Oncol 27(34):5848–5856PubMedCrossRefGoogle Scholar
  11. 11.
    Valastyan S, Reinhardt F, Benaich N et al (2009) A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 137(6):1032–1046PubMedCrossRefGoogle Scholar
  12. 12.
    Korpal M, Ell BJ, Buffa FM et al (2011) Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med 17(9):0–8CrossRefGoogle Scholar
  13. 13.
    Schlitt HJ, Neipp M, Weimann A et al (1999) Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation. J Clin Oncol 17(1):324–331PubMedGoogle Scholar
  14. 14.
    Han ZB, Zhong L, Teng MJ et al (2012) Identification of recurrence-related microRNAs in hepatocellular carcinoma following liver transplantation. Mol Oncol 6(4):445–457PubMedCrossRefGoogle Scholar
  15. 15.
    Yao FY, Ferrell L, Bass NM et al (2001) Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33(6):1394–1403PubMedCrossRefGoogle Scholar
  16. 16.
    Anglicheau D, Sharma VK, Ding R et al (2009) MicroRNA expression profiles predictive of human renal allograft status. Proc Natl Acad Sci 106(13):5330–5335PubMedCrossRefGoogle Scholar
  17. 17.
    Gupta GP, Massagué J (2006) Cancer metastasis: building a framework. Cell 127(4):679–695PubMedCrossRefGoogle Scholar
  18. 18.
    Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269PubMedCrossRefGoogle Scholar
  19. 19.
    Garzon R, Calin GA, Croce CM (2009) MicroRNAs in cancer. Annu Rev Med 60:167–179PubMedCrossRefGoogle Scholar
  20. 20.
    Huang S, He X (2010) The role of microRNAs in liver cancer progression. Br J Cancer 104(2):235–240PubMedCrossRefGoogle Scholar
  21. 21.
    Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449(7163):682–688PubMedCrossRefGoogle Scholar
  22. 22.
    Bhaumik D, Scott G, Schokrpur S, Patil C, Campisi J, Benz C (2008) Expression of microRNA-146 suppresses NF-κB activity with reduction of metastatic potential in breast cancer cells. Oncogene 27(42):5643–5647PubMedCrossRefGoogle Scholar
  23. 23.
    Wong CCL, Wong CM, Tung EKK et al (2011) The MicroRNA miR-139 suppresses metastasis and progression of hepatocellular carcinoma by down-regulating Rho-Kinase 2. Gastroenterology 140(1):322–331PubMedCrossRefGoogle Scholar
  24. 24.
    Yao J, Liang L, Huang S et al (2010) MicroRNA-30d promotes tumor invasion and metastasis by targeting Galphai2 in hepatocellular carcinoma. Hepatology 51(3):846–856PubMedGoogle Scholar
  25. 25.
    Budhu A, Jia HL, Forgues M et al (2008) Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology 47(3):897–907PubMedCrossRefGoogle Scholar
  26. 26.
    Wong QWL, Lung RWM, Law PTY et al (2008) MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of stathmin 1. Gastroenterology 135(1):257–269PubMedCrossRefGoogle Scholar
  27. 27.
    Huang XH, Wang Q, Chen JS et al (2009) Bead-based microarray analysis of microRNA expression in hepatocellular carcinoma: miR-338 is downregulated. Hepatol Res 39(8):786–794PubMedCrossRefGoogle Scholar
  28. 28.
    Tavazoie SF, Alarcon C, Oskarsson T et al (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451(7175):147–152PubMedCrossRefGoogle Scholar
  29. 29.
    Liu B, Peng XC, Zheng XL, Wang J, Qin YW (2009) MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer 66(2):169–175PubMedCrossRefGoogle Scholar
  30. 30.
    Feng R, Chen X, Yu Y et al (2010) miR-126 functions as a tumour suppressor in human gastric cancer. Cancer Lett 298(1):50–63PubMedCrossRefGoogle Scholar
  31. 31.
    Hamada S, Satoh K, Fujibuchi W et al (2011) miR-126 acts as a tumor suppressor in pancreatic cancer cells via the regulation of ADAM9. Mol Cancer Res. doi: 10.1158/1541-7786.mcr-11-0272 PubMedGoogle Scholar
  32. 32.
    Mazzaferro V, Regalia E, Doci R et al (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334(11):693–699PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Hongyuan Chen
    • 1
  • Ruizheng Miao
    • 2
  • Junwei Fan
    • 1
  • Zhongbo Han
    • 3
  • Junyi Wu
    • 1
  • Guoqiang Qiu
    • 1
  • Huamei Tang
    • 4
  • Zhihai Peng
    • 1
    Email author
  1. 1.Department of General SurgeryShanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina
  2. 2.Department of General SurgeryProvincial Hospital Affiliated To Shandong UniversityJinanChina
  3. 3.Department of General SurgeryCentral Hospital of Zi BoZi BoChina
  4. 4.Department of PathologyShanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina

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