LINC00152 Promotes Invasion through a 3'-Hairpin Structure and Associates with Prognosis in Glioblastoma.
LINC00152 Promotes Invasion through a 3'-Hairpin Structure and Associates with Prognosis in Glioblastoma.
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DOI：
10.1158/1541-7786.mcr-18-0322
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发表时间：
2018-10
期刊：
影响因子：
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通讯作者：
Dutta A
中科院分区：
文献类型：
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作者：
Reon BJ;Takao Real Karia B;Kiran M;Dutta A
长链非编码rna （lncRNAs）越来越多地参与肿瘤发生。本研究确定，LINC00152/CYTOR在多型胶质母细胞瘤（GBM）和侵袭性野生型IDH1/2级II/III级胶质瘤中表达上调，且上调与患者预后不良相关。LINC00152在超过10种其他癌症类型中同样上调，并与7种其他癌症类型的不良预后相关。细胞质LINC00152的抑制减弱，过表达增加细胞侵袭。LINC00152的敲低改变了上皮细胞到间质转化（EMT）的重要基因的转录。PARIS和Ribo-seq数据，以及二级结构预测，在LINC00152的3 '端发现了一个蛋白结合的121bp茎环结构，其过表达足以增加GBM细胞的侵袭。茎环中的点突变表明，发夹中的茎形成对LINC00152的功能至关重要。LINC00152具有几乎相同的同系物MIR4435-2HG，它编码一个几乎相同的发夹，在低级别胶质瘤（LGG）和GBM中同样表达，预测这些肿瘤患者的生存率较低，并且也被LINC00152敲低而降低。总之，这些数据揭示了LINC00152及其同系物MIR4435-2HG与侵袭性肿瘤相关，并通过一种需要发夹结构完整性的机制促进细胞侵袭。lncRNA LINC00152在胶质母细胞瘤和其他肿瘤类型中频繁上调，结合其预后潜力和促进侵袭的能力，表明LINC00152是一种潜在的生物标志物和治疗靶点。
Long non-coding RNAs (lncRNAs) are increasingly implicated in oncogenesis. Here, it is determined that LINC00152/CYTOR is upregulated in glioblastoma multiforme (GBM) and aggressive wild-type IDH1/2 grade II/III gliomas and upregulation associates with poor patient outcomes. LINC00152 is similarly upregulated in over 10 other cancer types and associates with a poor prognosis in 7 other cancer types. Inhibition of the mostly cytoplasmic LINC00152 decreases, and overexpression increases cellular invasion. LINC00152 knockdown alters the transcription of genes important to epithelial-to-mesenchymal transition (EMT). PARIS and Ribo-seq data, together with secondary structure prediction, identified a protein bound 121bp stem-loop structure at the 3′ end of LINC00152 whose overexpression is sufficient to increase invasion of GBM cells. Point mutations in the stem-loop suggest that stem formation in the hairpin is essential for LINC00152 function. LINC00152 has a nearly identical homolog, MIR4435-2HG, which encodes a near identical hairpin, is equally expressed in low-grade glioma (LGG) and GBM, predicts poor patient survival in these tumors and is also reduced by LINC00152 knockdown. Together, these data reveal that LINC00152 and its homolog MIR4435-2HG associate with aggressive tumors and promote cellular invasion through a mechanism that requires the structural integrity of a hairpin structure. Frequent upregulation of the lncRNA, LINC00152, in glioblastoma and other tumor types combined with its prognostic potential and ability to promote invasion suggests LINC00152 as a potential biomarker and therapeutic target.