LncRNA NEAT1 promotes colorectal cancer cell proliferation and migration via regulating glial cell-derived neurotrophic factor by sponging miR-196a-5p
LncRNA NEAT1 promotes colorectal cancer cell proliferation and migration via regulating glial cell-derived neurotrophic factor by sponging miR-196a-5p
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LncRNA NEAT1通过海绵miR-196a-5p调节胶质细胞源性神经营养因子促进结直肠癌细胞增殖和迁移
DOI：
10.1093/abbs/gmy130
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发表时间：
2018-12-01
影响因子：
3.7
通讯作者：
Chen, Cheng
中科院分区：
文献类型：
--
作者：
Zhong, Feng;Zhang, Wei;Chen, Cheng
结直肠癌（Colorectal cancer，CRC）是世界范围内最常见的恶性肿瘤之一。近年来，发现了广泛存在的长链非编码RNA（lncRNA），并且已知其在癌症中调节基因表达。然而，lncRNA在CRC中的作用和潜在机制仍不清楚。本研究通过CCK-8和transwell实验，首次发现抑制ncRNA核斑点组装转录本1（NEAT 1）抑制HCT 116细胞的增殖和迁移，过表达NEAT 1促进SW 480细胞的增殖和迁移。然后，我们发现抑制NEAT 1增加HCT 116细胞中miR-196 a-5 p的表达，而升高NEAT 1降低SW 480细胞中miR-196 a-5 p的表达。此外，miR-196 a-5 p可与NEAT 1的预测结合位点结合。然后我们发现miR-196 a-5 p参与了NEAT 1在CRC中的作用。此外，我们还通过qPCR和western blot分析证明，miR-196 a-5 p模拟物抑制了HCT 116细胞中胶质细胞源性神经营养因子（GDNF）的表达，同时，miR-196 a-5 p抑制剂促进了SW 480细胞中GDNF的表达。证明miR-196 a-5 p通过调控GDNF的表达发挥作用。最终，我们的研究表明NEAT 1通过miR-196 a-5 p/GDNF轴在CRC中发挥作用。总之，这项工作提供了CRC中NEAT 1/miR-196 a-5 p/GDNF调控通路的第一个证据。
Colorectal cancer (CRC) is the one of the most common malignant tumors worldwide. Recent years, widespread long non-coding RNAs (lncRNAs) have been discovered and are known to regulate gene expression in cancers. However, the roles and underlying mechanisms of lncRNA in CRC remain largely unclear. Here, we firstly revealed that repression of lncRNA nuclear para-speckle assembly transcript 1 (NEAT1) inhibited cell proliferation and migration in HCT116 cells and overexpression of NEAT1 promoted cell proliferation and migration in SW480 cells using CCK8 assay and transwell assay. Then, we found that suppression of NEAT1 increased the miR196a-5p expression in HCT116 cells, while elevation of NEAT1 decreased the miR-196a-5p expression in SW480 cells using qPCR assay. Furthermore, miR-196a-5p could bind to the predicted binding site of NEAT1. We then found that miR-196a-5p was involved in the role of NEAT1 in CRCs. In addition, we demonstrated that miR-196a-5p mimics inhibited the glial cell-derived neurotrophic factor (GDNF) expression in HCT116 cells and meanwhile, miR-196a-5p inhibitor promoted GDNF expression in SW480 cells using qPCR and western blot analysis. Then, we proved that miR-196a-5p exerted its function via regulating GDNF expression in CRCs. Ultimately, our study demonstrated that NEAT1 exerted its role via miR-196a-5p/GDNF axis in CRCs. In summary, this work provided the first evidence of a NEAT1/miR-196a-5p/GDNF regulatory pathway in CRC.