Long noncoding RNA NEAT1-modulated miR-506 regulates gastric cancer development through targeting STAT3
Long noncoding RNA NEAT1-modulated miR-506 regulates gastric cancer development through targeting STAT3
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长非编码RNA NEAT1调节的miR-506通过靶向STAT3调节胃癌的发展
DOI：
10.1002/jcb.26691
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发表时间：
2019-04-01
影响因子：
4
通讯作者：
Zhou, Xiang
中科院分区：
文献类型：
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作者：
Tan, Hai-Yang;Wang, Changcheng;Zhou, Xiang
越来越多的证据表明，长非编码RNA NEAT 1在癌症中发挥关键作用。迄今为止，NEAT 1在人类胃癌（GC）中的详细生物学作用和机制仍在很大程度上未知。在此，我们观察到与正常胃上皮细胞GES-1相比，NEAT 1和STAT 3在人GC细胞包括BGC 823、SGC-7901、AGS、MG C803和MKN 28细胞中的表达显著上调，而miR-506则下调。我们抑制NEAT 1，观察到NEAT 1抑制能够抑制GC细胞的生长、迁移和侵袭。相反，NEAT 1过表达在BGC 823和SGC-7901细胞中表现出增加的GC进展能力。生物信息学分析、双荧光素酶报告基因测定、RIP测定和RNA下拉测试验证了NEAT 1和miR-506之间的负结合相关性。此外，发现miR-506可以在体外调节NEAT 1的表达。STAT 3被预测为miR-506的信使RNA（mRNA）靶标，并且miR-506模拟物可以抑制STAT 3 mRNA表达。随后，观察到NEAT 1的下调可以通过减少STAT 3来抑制GC的发展，这可以被miR-506抑制剂逆转。因此，在我们的研究中假设NEAT 1可以被识别为竞争性内源性RNA，通过在GC中吸收miR-506来调节STAT 3。NEAT 1可作为胃癌诊断和治疗的重要生物标志物。
Accumulating evidence has indicated that long noncoding RNA NEAT1 exerts critical roles in cancers. So far, the detailed biological role and mechanisms of NEAT1, which are responsible for human gastric cancer (GC), are still largely unknown. Here, we observed that NEAT1 and STAT3 expressions were significantly upregulated in human GC cells including BGC823, SGC-7901, AGS, MGC803, and MKN28 cells compared with normal gastric epithelial cells GES-1, while miR-506 was downregulated. We inhibited NEAT1 and observed that NEAT1 inhibition was able to repress the growth, migration, and invasion of GC cells. Conversely, overexpression of NEAT1 exhibited an increased ability of GC progression in BGC823 and SGC-7901 cells. Bioinformatics analysis, dual luciferase reporter assays, RIP assays, and RNA pull-down tests validated the negative binding correlation between NEAT1 and miR-506. In addition, it was found that miR-506 can modulate the expression of NEAT1 in vitro. STAT3 was predicted as a messenger RNA (mRNA) target of miR-506, and miR-506 mimics can suppress STAT3 mRNA expression. Subsequently, it was observed that downregulation of NEAT1 can restrain GC development by decreasing STAT3, which can be reversed by miR-506 inhibitors. Therefore, it was hypothesized in our study that NEAT1 can be recognized as a competing endogenous RNA to modulate STAT3 by sponging miR-506 in GC. In conclusion, we implied that NEAT1 can serve as an important biomarker in GC diagnosis and treatment.