Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation
Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation
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DOI：
10.1007/s12032-011-0004-z
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发表时间：
2012-09-01
期刊：
影响因子：
3.4
通讯作者：
Zheng, Shu-sen
中科院分区：
文献类型：
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作者：
Lai, Ming-chun;Yang, Zhe;Zheng, Shu-sen
转移相关肺腺癌转录本1（MALAT1）是一种长链非编码RNA（lncRNA），在许多实体瘤中表达上调，与肿瘤转移和复发相关。然而，其在肝细胞癌（HCC）中的作用仍然知之甚少。在本研究中，我们评估了MALAT1的表达在9个肝癌细胞系和112例肝癌患者，包括60例接受肝移植（LT）完整的随访数据，通过定量实时PCR。此外，使用小干扰RNA（siRNA）来抑制MALAT1表达，以研究其在肿瘤进展中的生物学作用。我们发现MALAT1在细胞系和临床组织样本中均上调。MALAT1高表达的患者在LT后肿瘤复发的风险显著增加，特别是超过米兰标准的患者。多因素分析显示，MALAT1是预测肝癌复发的独立预后因素（危险比，3.280，P = 0.003）。此外，抑制MALAT1基因的表达可有效降低HepG2细胞的活力、运动性和侵袭性，并增加细胞对凋亡的敏感性。我们的数据表明，lncRNA MALAT1在肿瘤进展中起重要作用，可能是预测LT后肿瘤复发的新生物标志物，并作为一个有前途的治疗靶点。
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.