Upregulation of long noncoding RNA zinc finger antisense 1 enhances epithelial-mesenchymal transition in vitro and predicts poor prognosis in glioma
Upregulation of long noncoding RNA zinc finger antisense 1 enhances epithelial-mesenchymal transition in vitro and predicts poor prognosis in glioma
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DOI：
10.1177/1010428317695022
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发表时间：
2017-03-01
期刊：
影响因子：
--
通讯作者：
Zhou, Hong-Hao
中科院分区：
文献类型：
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作者：
Lv, Qiao-Li;Chen, Shu-Hui;Zhou, Hong-Hao
越来越多的证据表明，长链非编码RNA在各种癌症的发生和发展中起着重要作用。锌指反义1是一种新型的长链非编码RNA，其在胶质瘤中的临床意义、生物学功能和作用机制尚不清楚。在本研究中，我们报道了锌指反义1在胶质瘤中的表达显著上调，并与临床分期密切相关。此外，锌指反义1高表达的患者生存期较短。多因素考克斯回归分析提示锌指反义1表达水平可能是胶质瘤的独立预后因素。在功能上，锌指反义1作为一种癌基因在胶质瘤中发挥作用，因为它的敲低可以促进细胞凋亡，并显著抑制细胞增殖、迁移和侵袭。反义锌指1基因沉默可使U87和U251细胞周期阻滞于G 0/G1期，S期细胞比例相应降低。此外，发现沉默锌指反义1通过降低MMP 2、MMP 9、N-cadherin、Integrin beta 1、ZEB 1、Twist和Snail的表达以及增加E-cadherin水平来抑制胶质瘤中的上皮-间质转化，从而损害迁移和侵袭。综上所述，我们的数据表明，锌指反义1可能作为一个有价值的预后生物标志物和潜在的治疗靶点胶质瘤。
Increasing evidence indicates that long noncoding RNAs play important roles in development and progression of various cancers. Zinc finger antisense 1 is a novel long noncoding RNA whose clinical significance, biological function, and underlying mechanism are still undetermined in glioma. In this study, we reported that zinc finger antisense 1 expression was markedly upregulated in glioma and tightly correlated with clinical stage. Moreover, patients with high zinc finger antisense 1 expression had shorter survival. Multivariate Cox regression analysis provided a clue that, probably, zinc finger antisense 1 level could serve as an independent prognostic factor for glioma. Functionally, zinc finger antisense 1 acted as an oncogene in glioma because its knockdown could promote apoptosis and significantly inhibit cell proliferation, migration, and invasion. Furthermore, zinc finger antisense 1 silencing could result in cell cycle arrest at the G0/G1 phase and correspondingly decrease the percentage of S phase cells in both U87 and U251 cell lines. Moreover, it was found that silenced zinc finger antisense 1 could impair migration and invasion by inhibiting the epithelial-mesenchymal transition through reducing the expression of MMP2, MMP9, N-cadherin, Integrin beta 1, ZEB1, Twist, and Snail as well as increasing E-cadherin level in glioma. Taken together, our data identified that zinc finger antisense 1 might act as a valuable prognostic biomarker and potential therapeutic target for glioma.