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长链非编码 RNA TRERNA1 水平升高与 HIF-1α 的激活相关,可预测肝细胞癌的预后不良。

Elevated LncRNA TRERNA1 correlated with activation of HIF-1α predicts poor prognosis in hepatocellular carcinoma.

机构信息

Department of Medical Genetics and Developmental Biology, Medical School of Southeast University, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, 87# Dingjiaqiao, Gulou District, Nanjing 210009, Jiangsu, China.

Department of Pathology, Medical School, Southeast University, 87# Dingjiaqiao, Gulou District, Nanjing 210009, Jiangsu, China.

出版信息

Pathol Res Pract. 2021 Nov;227:153612. doi: 10.1016/j.prp.2021.153612. Epub 2021 Sep 11.

Abstract

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-1α and E-cadherin. χ 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-1α. Importantly, high TRERNA1 expression level can be an independent risk factor for poor prognosis in HCC, especially combining elevated TRERNA1 and HIF-1α 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-1α and E-cadherin.

摘要

背景

据报道,转录调控长非编码 RNA 1(TRERNA1)在多种癌症中上调,并通过诱导上皮-间充质转化(EMT)加速肿瘤转移。然而,TRERNA1 如何上调以及 TRERNA1 的上调是否影响 HCC 患者的预后尚不清楚。在本研究中,我们旨在探讨 TRERNA1 在 HCC 中的预后价值以及 TRERNA1 上调的调控机制。

方法

采用原位杂交分析 TRERNA1 的表达水平,免疫组织化学技术评估 HIF-1α 和 E-钙黏蛋白的表达水平。χ检验评估 TRERNA1 水平与 HCC 病例临床病理特征的关系,Kaplan-Meier 生存分析、ROC 曲线分析和 Cox 比例风险回归模型评估 TRERNA1 表达水平在 HCC 中的预后意义。

结果

TRERNA1 在 HCC 组织中显著上调,同时伴有 E-钙黏蛋白的异常下调。升高的 TRERNA1 水平与 HCC 患者的高肿瘤分级、高复发率和不良生存相关。此外,TRERNA1 表达水平与 HIF-1α 的激活呈正相关。重要的是,高 TRERNA1 表达水平是 HCC 患者预后不良的独立危险因素,尤其是结合升高的 TRERNA1 和 HIF-1α 与降低的 E-钙黏蛋白可预测 HCC 患者的最差预后。

结论

TRERNA1 不仅是预测 HCC 患者预后不良的生物标志物,还可以与 HIF-1α 和 E-钙黏蛋白结合,将 HCC 患者分为不同的生存风险组。

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