The long non-coding RNA Linc-GALH promotes hepatocellular carcinoma metastasis via epigenetically regulating Gankyrin
The long non-coding RNA Linc-GALH promotes hepatocellular carcinoma metastasis via epigenetically regulating Gankyrin
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长链非编码RNA Linc-GALH通过表观遗传调控Gankyrin促进肝细胞癌转移
DOI：
10.1038/s41419-019-1348-0
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发表时间：
2019-01-28
影响因子：
9
通讯作者：
Tan, Zhongming
中科院分区：
文献类型：
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作者：
Xu, Xiaoliang;Lou, Yun;Tan, Zhongming
肝细胞癌是肝癌中最常见的亚型，具有高转移率和复发率的特点。最近的研究加深了我们对Gankyrin在这两种病理特性中的作用的理解，但其异常调控的机制尚不清楚。近年来，许多长非编码RNA(LncRNAs)被报道通过多种机制参与调控癌基因和抑癌基因的表达。在这里，利用转录微阵列分析，我们发现了一个称为Linc-GALH的长长的基因间非编码RNA，它在肝细胞癌中高表达，并与Gankyrin的表达一致。此外，我们还发现Linc-GALH是一个独立的预后不良指标，后续的功能实验表明Linc-GALH在体外促进了肝癌细胞的迁移和侵袭，并增强了肝癌细胞在体内的肺转移能力。从机制上，我们发现Linc-GALH可以通过调节肝细胞癌中DNMT1的泛素化状态来控制Gankyrin的甲基化状态，从而调节Gankyrin的表达。总之，我们的结果证实了Linc-GALH在肝癌中的作用和作用机制，并表明Linc-GALH可能作为一种预测肝癌预后的生物标志物和潜在的治疗靶点。
Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer, and it is characterized by high rate of metastasis and recurrence. Recent studies have boosted our understanding that Gankyrin contributes to both of these pathological properties, but the mechanisms underlying its aberrant regulation are poorly understood. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in regulating the expression of oncogenes and anti-oncogenes through various mechanisms. Here, using transcriptome microarray analysis, we identified a long intergenic noncoding RNA termed Linc-GALH that was highly expressed and concordance with Gankyrin expression in HCC. In addition, we revealed that Linc-GALH was an independent unfavorable prognostic indicator for HCC, followed functional experiments showed that Linc-GALH promoted HCC cells migration and invasion in vitro, and enhanced lung metastasis ability of HCC cells in vivo. Mechanistically, we found that Linc-GALH could regulate the expression of Gankyrin through controlling the methylation status of Gankyrin by adjusting the ubiquitination status of DNMT1 in HCC. Collectively, our results demonstrated the role and functional mechanism of Linc-GALH in HCC, and indicated that Linc-GALH may act as a prognostic biomarker and potential therapeutic target for HCC.