长链非编码RNA NEAT1通过与G9a-DNMT1-Snail复合物相互作用促进骨肉瘤转移。
Long noncoding RNA NEAT1 promotes the metastasis of osteosarcoma via interaction with the G9a-DNMT1-Snail complex.
作者信息
Li Yong, Cheng Cai
机构信息
Department of Orthopedics, Cangzhou Central HospitalCangzhou, China.
出版信息
Am J Cancer Res. 2018 Jan 1;8(1):81-90. eCollection 2018.
Abstract
Osteosarcoma (OS) is the most common histological form of primary bone cancer. Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) functions as an oncogene in some cancers. However, the functional role of NEAT1 in OS metastasis remains elusive. In the present study, we found that NEAT1 expression was significantly increased in OS tissues and cell lines. Overexpression of NEAT1 in OS tissues was correlated with higher clinical stage, distant metastasis and poorer prognosis. Loss- and gain-of-function assays showed that NEAT1 positively regulated metastasis and . In addition, ectopic expression of NEAT1 also induced epithelial-mesenchymal transition (EMT). Mechanistic studies revealed that NEAT1 epigenetically suppresses E-cadherin expression through association with G9a-DNMT1-Snail complex. Taken together, our study reveals a critical epigenetic mechanism underlying NEAT1-mediated metastasis.
摘要
骨肉瘤（OS）是原发性骨癌最常见的组织学形式。长链非编码RNA核富集丰富转录本1（NEAT1）在某些癌症中作为癌基因发挥作用。然而，NEAT1在骨肉瘤转移中的功能作用仍不清楚。在本研究中，我们发现骨肉瘤组织和细胞系中NEAT1表达显著增加。骨肉瘤组织中NEAT1的过表达与更高的临床分期、远处转移和更差的预后相关。功能缺失和功能获得实验表明，NEAT1正向调节转移。此外，NEAT1的异位表达还诱导上皮-间质转化（EMT）。机制研究表明，NEAT1通过与G9a-DNMT1-Snail复合物结合，在表观遗传上抑制E-钙黏蛋白的表达。综上所述，我们的研究揭示了NEAT1介导转移的关键表观遗传机制。
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