Long non-coding RNA DANCR stabilizes HIF-1α and promotes metastasis by interacting with NF90/NF45 complex in nasopharyngeal carcinoma
Long non-coding RNA DANCR stabilizes HIF-1α and promotes metastasis by interacting with NF90/NF45 complex in nasopharyngeal carcinoma
复制标题
长非编码 RNA DANCR 通过与鼻咽癌中的 NF90/NF45 复合物相互作用来稳定 HIF-1α 并促进转移
DOI：
10.7150/thno.28538
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发表时间：
2018-01-01
期刊：
影响因子：
12.4
通讯作者：
Li, Ying-Qin
中科院分区：
文献类型：
--
作者：
Wen, Xin;Liu, Xu;Li, Ying-Qin
长链非编码RNA（lncRNA）在肿瘤的发生、发展中起着重要作用。方法：采用定量RT-PCR方法检测鼻咽癌组织中DANCR的表达，Kaplan-Meier曲线分析DANCR表达与鼻咽癌预后的关系。进行RNA测序，然后进行生物信息学分析，以确定DANCR的潜在功能。通过体外和体内实验研究其生物学效应。DANCR相互作用的蛋白质通过RNA pull-down检测，然后通过质谱和蛋白质印迹法进行鉴定，然后通过RNA免疫沉淀（RIP）检测进行确认。我们发现DANCR在NPC中表达上调，尤其是在有淋巴矿脉转移的NPC中，其表达上调可能预示生存不良。然后我们建立了一个预后预测模型。RNA测序和生物信息学分析表明，DANCR与NPC的转移和缺氧表型有关。功能研究表明，DANCR在体内外均能促进鼻咽癌细胞的侵袭和转移。进一步研究表明，DANCR可通过与NF 90/NF 45复合物相互作用，增加HIF-1 α mRNA的稳定性。此外，HIF-1 α在DANCR敲低细胞中的过表达恢复了其对NPC细胞迁移和invasion.Conclusions的抑制作用：两者合计，我们的研究结果表明，DANCR作为一种预后生物标志物，并通过与NF 90/NF 45相互作用增加HIF-1 α mRNA的稳定性，导致NPC的转移和疾病进展。
Long noncoding RNAs (lncRNAs) play an important role in the development and progression of cancers. However, the clinical significances of lncRNAs and their functions and mechanisms in nasopharyngeal carcinoma (NPC) remain largely unclear.Methods: Quantitative RT-PCR was used to determine DANCR expression and Kaplan-Meier curves were used to evaluate its prognostic value. RNA sequencing followed by bioinformatic analysis was performed to determine the potential function of DANCR. In vitro and in vivo experiments were conducted to investigate its biological effects. DANCR-interacting proteins were identified by RNA pull-down assay followed by mass spectrometry and western blotting, and then confirmed by RNA immunoprecipitation (RIP) assays.Results: Our previous microarray analysis identified a metastasis-associated lncRNA DANCR. Here, we found that DANCR was upregulated in NPC, especially in those with lymph lode metastasis, and its upregulation could predict poor survival. We then constructed a prognostic predictive model. RNA sequencing followed by bioinformatic analysis revealed that DANCR was responsible for NPC metastasis and hypoxia phenotype. Functional studies showed that DANCR promoted NPC cell invasion and metastasis in vitro and in vivo. Further investigation suggested that DANCR could increase HIF-1 alpha mRNA stability through interacting with the NF90/NF45 complex. Additionally, overexpression of HIF-1 alpha in DANCR knockdown cells restored its suppressive effects on NPC cell migration and invasion.Conclusions: Taken together, our results suggest that DANCR acts as a prognostic biomarker and increases HIF-1 alpha mRNA stability by interacting with NF90/NF45, leading to metastasis and disease progression of NPC.