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

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.

Expression and Prognostic Significance of lncRNA MALAT1 in Pancreatic Cancer Tissues

“…Multivariate analysis further showed that expression of MALAT1, together with tumor location and nervous invasion, was an independent predictor of disease specific survival for PDAC. This was in agreement with the prognostic role of MALAT1 in colorectal cancer (Ji et al, 2013), HCC (Lai et al, 2012) and NSCLC (Schmidt et al, 2011). Thus, high MALAT1 expression in several tumors was associated with a poor prognosis and MALAT1 could act as an independent prognostic factor for predicting tumor prognosis, including PDAC.…”

Epigenetics in Liver Disease

“…32 MALAT1 is a very large (8,000 nt) nuclear lncRNA expressed in HCC and is associated with high risk of posttransplant recurrence. 33 Knockdown of MALAT1 in HCC cell lines has similar behavioral effects to those described for depletion of HOTAIR. Future work with lncRNAs is greatly anticipated and expected to lead to exciting new insights into hepatic gene regulation.…”

The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine

“…[39][40][41][42][43] In addition, increased expression of MALAT1 has been recently shown to be an independent prognostic factor for HCC following liver transplantation. 44 Notably, the MALAT1 locus at 11q13.1 has been identified to harbor chromosomal translocation breakpoints associated with cancer. [45][46][47] Following the correlation between high levels of MALAT1 expression and cancer, a number of studies have implicated MALAT1 in the regulation of cell mobility.…”