NEAT1 Negatively Regulates Cell Proliferation and Migration of Neuroblastoma Cells by miR-183-5p/FOXP1 Via the ERK/AKT Pathway.
NEAT1 Negatively Regulates Cell Proliferation and Migration of Neuroblastoma Cells by miR-183-5p/FOXP1 Via the ERK/AKT Pathway.
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NEAT1 通过 ERK/AKT 途径通过 miR-183-5p/FOXP1 负向调节神经母细胞瘤细胞的增殖和迁移
DOI：
10.1177/0963689720943608
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发表时间：
2020-01
影响因子：
3.3
通讯作者：
Li P
中科院分区：
文献类型：
--
作者：
Pan W;Wu A;Yu H;Yu Q;Zheng B;Yang W;Tian D;Gao Y;Li P
神经母细胞瘤是一种交感神经系统的恶性肿瘤，是儿童时期侵袭性的颅外肿瘤。长非编码RNA(LncRNAs)在真核生物调控基因网络中起着关键作用，参与了多种生物学过程。我们观察到LncRNA核富含转录因子1(NEAT1)在人神经母细胞瘤组织和细胞系中的表达显著低于正常组织。采用细胞计数试剂盒8法、集落形成实验和Transwell实验观察NEAT1、miR-183-5p和Foxp1对神经母细胞瘤细胞增殖、迁移和侵袭能力的影响。我们还利用Starbase和荧光素酶报告基因分析来预测和证实NEAT1、miR-183-5p和Foxp1在神经母细胞瘤细胞中的相互作用。首先，NEAT1的过表达抑制了细胞的增殖，并在细胞的迁移和侵袭中发挥了关键作用。此外，NEAT1还与miR-183-5p直接相互作用，并通过负向调节miR-183-5p的表达而发挥抗神经母细胞瘤的作用。MIR-183-5p通过直接靶向Foxp1mRNA3‘非翻译区，抑制Foxp1的表达，调节细胞的增殖和迁移。此外，Foxp1可拮抗miR-183-5p对神经母细胞瘤细胞外调节的蛋白激酶/蛋白激酶B(ERK/AKT)磷酸化的影响，而Foxp1 siRNA可增强miR-183-5p抑制剂引起的ERK/AKT磷酸化水平的降低。综上所述，这些数据表明，NEAT1通过抑制ERK/AKT通路，通过miR-183-5p/Foxp1轴负性调控神经母细胞瘤的细胞增殖和迁移。我们的发现可能为研究神经母细胞瘤的发病机制和治疗提供新的靶点。
Neuroblastoma, a malignant tumor of the sympathetic nervous system, is an aggressive extracranial tumor in childhood. Long noncoding RNAs (lncRNAs) have been discovered to play a key role in the eukaryotic regulatory gene network and be involved in a wide variety of biological processes. We observed that the expression of lncRNA nuclear-enriched abundant transcript-1 (NEAT1) was significantly decreased in human neuroblastoma tissues and cell lines, compared with the normal. We observed cell proliferation, migration, and invasion with Cell Counting Kit-8 assay, colony formation assay, and Transwell assay to investigate the effects of NEAT1, miR-183-5p, or FOXP1 on neuroblastoma cells. And we also used StarBase and luciferase reporter gene assay to predict and confirm the interaction of NEAT1, miR-183-5p, and FOXP1 in neuroblastoma cells. First, overexpression of NEAT1 suppressed cell proliferation and played a key role in cell migration and invasion. In addition, NEAT1 was demonstrated to directly interact with miR-183-5p and exerted its antioncogenic role in neuroblastoma by negatively regulating miR-183-5p expression. miR-183-5p suppressed the expression of FOXP1 and regulated cell proliferation and migration by directly targeting FOXP1 mRNA 3′-untranslated region. Moreover, FOXP1 antagonized the effect of miR-183-5p on the phosphorylation of extracellular-regulated kinase/protein kinase B (ERK/AKT), while FOXP1 siRNA increased the reduced phosphorylation of ERK/AKT caused by miR-183-5p inhibitor in neuroblastoma cells. Taken together, these data showed that NEAT1 negatively regulated cell proliferation and migration of neuroblastoma by the miR-183-5p/FOXP1 axis via suppression of the ERK/AKT pathway. Our findings may provide a new target for the study of pathogenesis and treatment of neuroblastoma.
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影响因子：
2.9
作者：
Halacli SO;Dogan AL
通讯作者：
Dogan AL
影响因子：
11.2
作者：
Gomez GG;Volinia S;Croce CM;Zanca C;Li M;Emnett R;Gutmann DH;Brennan CW;Furnari FB;Cavenee WK
通讯作者：
Cavenee WK
影响因子：
5.3
作者：
Li, Ning;Wang, Hao;Li, Rui
通讯作者：
Li, Rui
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影响因子：
--
作者：
Zhang, Bao-Le;Dong, Fu-Lu;Gao, Dian-Shuai
通讯作者：
Gao, Dian-Shuai
影响因子：
4
作者：
Ding N;Wu H;Tao T;Peng E
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Peng E