Overexpression of Long Non-coding RNA HOTAIR Predicts Tumor Recurrence in Hepatocellular Carcinoma Patients Following Liver Transplantation
Overexpression of Long Non-coding RNA HOTAIR Predicts Tumor Recurrence in Hepatocellular Carcinoma Patients Following Liver Transplantation
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DOI：
10.1245/s10434-011-1581-y
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发表时间：
2011-05-01
影响因子：
3.7
通讯作者：
Zheng, Shu-Sen
中科院分区：
文献类型：
--
作者：
Yang, Zhe;Zhou, Lin;Zheng, Shu-Sen
据报道，长的非编码RNA HOTAIR是乳腺癌患者预后较差的生物标志物。为探讨HOTAIR在肝细胞癌中的表达模式及其临床意义及其在肿瘤进展中的生物学作用，采用实时荧光定量逆转录-聚合酶链式反应技术检测了110例肝细胞癌标本中HOTAIR的表达，并分析了其与肝细胞癌临床参数和预后的关系。利用siRNA抑制HOTAIR在肿瘤进展中的作用，发现HOTAIR在癌组织中的表达水平高于癌旁组织。HOTAIR的高表达水平是预测LT患者肝细胞癌复发的独立预后因素(P=.001，风险比，3.564)。此外，在超过米兰标准的患者中，HOTAIR高表达水平的患者无复发生存期显著缩短。此外，抑制肝癌细胞株中HOTAIR的siRNA表达可降低细胞存活率和侵袭力，敏化肿瘤坏死因子-α诱导的细胞凋亡，增加癌细胞对顺铂和阿霉素的化疗敏感性。HOTAIR在肝癌中的高表达可作为预测肝移植患者肿瘤复发的候选生物标志物，并可能成为潜在的治疗靶点。
The long noncoding RNA HOTAIR has been reported as a poor prognostic biomarker in patients with breast cancer. The aim of the present study is to examine the expression pattern of HOTAIR in hepatocellular carcinoma (HCC) and its clinical significance as well as its biological role in tumor progression.We examined the expression of HOTAIR in 110 HCC samples using real-time reverse transcription-polymerase chain reaction and analyzed its correlation with clinical parameters and prognosis in 60 HCC patients that have undergone liver transplantation (LT). Suppression of HOTAIR using siRNA was performed to explore its roles in tumor progression.The expression level of HOTAIR in cancer tissues was higher than in adjacent noncancerous tissues. High expression level of HOTAIR was an independent prognostic factor for predicting HCC recurrence in LT patients (P = .001, hazard ratio, 3.564). Furthermore, in patients exceeding the Milan criteria, those with a high expression level of HOTAIR revealed a significantly shorter recurrence-free survival. Moreover, siRNA suppression of HOTAIR in a liver cancer cell line reduced cell viability and cell invasion, sensitized TNF-alpha induced apoptosis, and increased the chemotherapeutic sensitivity of cancer cells to cisplatin and doxorubicin.The high expression level of HOTAIR in HCC could be a candidate biomarker for predicting tumor recurrence in HCC patients who have undergone liver transplant therapy and might be a potential therapeutic target.