Elevated LncRNA TRERNA1 correlated with activation of HIF-1α predicts poor prognosis in hepatocellular carcinoma
Elevated LncRNA TRERNA1 correlated with activation of HIF-1α predicts poor prognosis in hepatocellular carcinoma
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DOI：
10.1016/j.prp.2021.153612
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发表时间：
2021-09-22
影响因子：
2.8
通讯作者：
Fan, Hong
中科院分区：
文献类型：
--
作者：
Qian, Yanyan;Li, Yiping;Fan, Hong
背景资料：翻译调控长链非编码RNA 1（translation regulatory long non-coding RNA 1，TRERNA 1）在多种肿瘤中表达上调，通过诱导上皮细胞向间质细胞转化（epithelial-to-mesenchymal transition，EMT）加速肿瘤转移。然而，目前还不清楚TRERNA 1是如何上调的，以及TRERNA 1的上调是否影响HCC患者的预后。本研究旨在探讨TRERNA 1在肝癌中的预后价值及其上调的调控机制，方法：采用原位杂交技术检测TRERNA 1的表达水平，免疫组化技术检测HIF-1 α和E-cadherin的表达水平。采用卡方检验（χ 2检验）分析TRERNA 1表达水平与HCC临床病理特征的关系，Kaplan-Meier生存分析、ROC曲线分析和考克斯比例风险回归模型分析TRERNA 1表达水平与HCC预后的关系。肝癌患者中TRERNA 1水平升高与高肿瘤分级、高复发率和低生存率相关。TRERNA 1的表达水平与HIF-1 α的激活呈正相关。值得注意的是，TRERNA 1高表达可能是HCC预后不良的独立危险因素，尤其是TRERNA 1和HIF-1 α的高表达与E-cadherin的低表达联合预测HCC患者的预后最差。TRERNA 1不仅是预测HCC患者预后不良的生物标志物，而且当与HIF-1 α和E-cadherin联合使用时，可以将HCC患者分为不同的生存风险组。
Background: Translation regulatory long non-coding RNA 1 (TRERNA1) has been reported to be upregulated in several cancers and accelerate tumor metastasis by inducing epithelial-to-mesenchymal transition (EMT). However, it remains unclear how TRERNA1 is upregulated and whether the upregulation of TRERNA1 influences the prognosis of HCC patients. In this study, we aimed to investigate the prognostic value of TRERNA1 in HCC and the regulatory mechanism underlying TRERNA1 upregulation.Methods: In situ hybridization was adopted to analyze the expression level of TRERNA1, and immunohistochemistry technique was employed to evaluate the expression level of HIF-1 alpha and E-cadherin. chi(2) test was used to assess the association between TRERNA1 level and clinicopathological characteristics of HCC cases, whereas Kaplan-Meier survival analysis, ROC curve analysis and Cox proportional hazards regression model were performed to evaluate the prognostic significance of TRERNA1 expression level in HCC.Results: TRERNA1 was substantially upregulated in HCC tissues, which was accompanied by aberrant decreased expression of E-cadherin. Elevated TRERNA1 level was correlated with high tumor grade, high recurrence rate and poor survival in patients with HCC. Moreover, TRERNA1 expression level was positively correlated with the activation of HIF-1 alpha. Importantly, high TRERNA1 expression level can be an independent risk factor for poor prognosis in HCC, especially combining elevated TRERNA1 and HIF-1 alpha with decreased E-cadherin predicted a worst prognosis of patients with HCC.Conclusion: TRERNA1 is not only a biomarker for predicting poor prognosis in HCC patients, but also can categorize HCC patients into different risk groups for survival when combined with HIF-1 alpha and E-cadherin.