LncRNA NR038975, A Serum-Based Biomarker, Promotes Gastric Tumorigenesis by Interacting With NF90/NF45 Complex.
LncRNA NR038975, A Serum-Based Biomarker, Promotes Gastric Tumorigenesis by Interacting With NF90/NF45 Complex.
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DOI：
10.3389/fonc.2021.721604
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhao L
中科院分区：
文献类型：
--
作者：
Wei S;Dai S;Zhang C;Zhao R;Zhao Z;Song Y;Shan B;Zhao L
胃癌是世界上最致命的恶性肿瘤之一，长链非编码RNA（lncRNA）是胃癌发生发展的重要调控因子。本研究在GC中鉴定了一种新的功能性lncRNA，命名为NR 038975，其在基因表达谱交互分析（GEPIA）数据集和我们的独立GC组织队列中被证实显著上调。我们首次鉴定了NR 038975的全长序列和在胃癌细胞中的亚细胞定位。我们的数据表明，NR 038975表达上调与淋巴结转移和TNM分期显著相关。此外，NR 038975的敲低抑制GC细胞增殖、迁移、侵袭和克隆形成，反之亦然。从机制上讲，RNA下拉和质谱分析鉴定了NR 038975结合蛋白和NF 90/NF 45复合物，并且还通过RNA免疫沉淀和共聚焦实验证实了结合。我们进一步证明了NR 038975的遗传缺陷消除了NF 45和NF 90之间的相互作用。此外，NF 90增加了NR 038975的稳定性。因此，NR 038975-NF 90/NF 45将是GC的重要组合靶点。最后，我们在血清外泌体和GC患者的血清中检测NR 038975。我们的研究结果表明，NR 038975是胃肿瘤发生的生物标志物。目前的研究表明，NR 038975是一种新的lncRNA，在临床和功能上参与GC进展，可能是一种新的诊断标志物和潜在的治疗靶点。
Gastric cancer (GC) is one of the deadliest cancers, and long noncoding RNAs (lncRNAs) have been reported to be the important regulators during the occurrence and development of GC. The present study identified a novel and functional lncRNA in GC, named NR038975, which was confirmed to be markedly upregulated in the Gene Expression Profiling Interactive Analysis (GEPIA) dataset and our independent cohort of GC tissues. We firstly characterized the full-length sequence and subcellular location of NR038975 in GC cells. Our data demonstrated that upregulated NR038975 expression was significantly related to lymph node metastasis and TNM stage. In addition, knockdown of NR038975 inhibited GC cell proliferation, migration, invasion, and clonogenicity and vice versa. Mechanistically, RNA pull-down and mass spectrometry assays identified the NR038975-binding proteins and NF90/NF45 complex, and the binding was also confirmed by RNA immunoprecipitation and confocal experiments. We further demonstrated that genetic deficiency of NR038975 abrogated the interaction between NF45 and NF90. Moreover, NF90 increased the stability of NR038975. Thus, NR038975-NF90/NF45 will be an important combinational target of GC. Finally, we detected NR038975 in serum exosomes and serum of GC patients. Our results indicated that NR038975 was a biomarker for gastric tumorigenesis. The current study demonstrated that NR038975 is a novel lncRNA that is clinically and functionally engaged in GC progression and might be a novel diagnostic marker and potential therapeutic target.
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DOI：
10.1126/science.1240925
发表时间：
2013-08-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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影响因子：
11.2
作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
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DOI：
10.1126/science.1237973
发表时间：
2013-08-16
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
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影响因子：
9
作者：
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