Original Paper

Medical Oncology

, Volume 29, Issue 3, pp 1810-1816

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

  • Ming-chun LaiAffiliated withDepartment of Hepatobiliary and Pancreatic Surgery, Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine
  • , Zhe YangAffiliated withDepartment of Hepatobiliary and Pancreatic Surgery, Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine
  • , Lin ZhouAffiliated withDepartment of Hepatobiliary and Pancreatic Surgery, Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine
  • , Qian-qian ZhuAffiliated withDepartment of Hepatobiliary and Pancreatic Surgery, Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine
  • , Hai-yang XieAffiliated withDepartment of Hepatobiliary and Pancreatic Surgery, Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine
  • , Feng ZhangAffiliated withDepartment of Hepatobiliary and Pancreatic Surgery, Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine
  • , Li-ming WuAffiliated withDepartment of Hepatobiliary and Pancreatic Surgery, Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine
  • , Lei-ming ChenAffiliated withDepartment of Hepatobiliary and Pancreatic Surgery, Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine
  • , Shu-sen ZhengAffiliated withDepartment of Hepatobiliary and Pancreatic Surgery, Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine Email author 

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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.

Keywords

MALAT1 Hepatocellular carcinoma Recurrence Transplantation Liver transplantation