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基因扩增产生了一种癌症-睾丸长非编码 RNA PCAT6,它调节肝癌中的细胞增殖和迁移。

Gene amplification derived a cancer-testis long noncoding RNA PCAT6 regulates cell proliferation and migration in hepatocellular carcinoma.

机构信息

Department of Epidemiology and Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

出版信息

Cancer Med. 2019 Jun;8(6):3017-3025. doi: 10.1002/cam4.2141. Epub 2019 Apr 9.

Abstract

Our previous work demonstrated cancer-testis (CT) genes as a new source of candidate driver of cancer. Recently, mounting evidence indicates that long noncoding RNAs (lncRNAs) with CT expression pattern could play a pivotal role in cancer biology. Here, we characterized a conserved CT long noncoding RNA (CT-lncRNA), PCAT6, which is expressed exclusively in the testis and is reactivated in liver hepatocellular carcinoma (LIHC) tissues due to the highly frequent amplification. The expression in LIHC was correlated with clinical prognosis in TCGA data. Knockdown of PCAT6 could inhibit cell proliferation and migration in hepatocellular carcinoma (LIHC) cells. Gene set enrichment analysis (GSEA) based on coexpression network revealed that PCAT6 was involved in similar cilium-related pathways in the testis and LIHC tissues. However, PCAT6 was mainly positively correlated with gametogenesis-related pathways in the testis but was coexpressed with mitotic cell cycle genes in LIHC. Together, our data demonstrated that CT-lncRNA PCAT6 represents the similarity and difference between tumorigenesis and gametogenesis. The CT expression pattern and important role in LIHC oncogenesis make PCAT6 an ideal target for LIHC diagnosis and therapy.

摘要

我们之前的工作表明,癌症睾丸(CT)基因是癌症驱动因子的新来源。最近,越来越多的证据表明,具有 CT 表达模式的长非编码 RNA(lncRNA)可能在癌症生物学中发挥关键作用。在这里,我们描述了一个保守的 CT 长非编码 RNA(CT-lncRNA),PCAT6,它仅在睾丸中表达,由于高度频繁的扩增,在肝癌(LIHC)组织中重新激活。在 TCGA 数据中,PCAT6 的表达与临床预后相关。PCAT6 的敲低可抑制肝癌(LIHC)细胞的增殖和迁移。基于共表达网络的基因集富集分析(GSEA)表明,PCAT6 参与了睾丸和 LIHC 组织中类似的纤毛相关途径。然而,PCAT6 在睾丸中主要与配子发生相关途径呈正相关,而在 LIHC 中与有丝分裂细胞周期基因共表达。总之,我们的数据表明,CT-lncRNA PCAT6 代表了肿瘤发生和配子发生之间的相似性和差异。CT 的表达模式和在 LIHC 致癌中的重要作用使 PCAT6 成为 LIHC 诊断和治疗的理想靶点。

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