LncRNA NEAT1 promotes proliferation, migration, invasion and epithelial-mesenchymal transition process in TGF-β2-stimulated lens epithelial cells through regulating the miR-486-5p/SMAD4 axis.
LncRNA NEAT1 promotes proliferation, migration, invasion and epithelial-mesenchymal transition process in TGF-β2-stimulated lens epithelial cells through regulating the miR-486-5p/SMAD4 axis.
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DOI：
10.1186/s12935-020-01619-8
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发表时间：
2020-10-31
影响因子：
5.8
通讯作者：
Zheng G
中科院分区：
文献类型：
--
作者：
Wang H;Zheng G
晶状体上皮细胞(LECs)的异常增殖、转移和上皮间质转化(EMT)是后囊混浊的直接因素。核富含转录本1(NEAT1)已被证明可促进细胞增殖、转移和EMT，但是否影响PCO的进展尚不清楚。用实时定量聚合酶链式反应(qRT-PCR)检测了NEAT1、microRNA-486-5p(miR-486-5p)和果蝇妈妈抗十面瘫4(Smad4)基因的表达。3-(4，5-二甲基-2-噻唑基)-2，5-二苯基-2-H-四唑溴化法测定细胞增殖。Transwell法检测细胞的迁移和侵袭能力。免疫印迹(WB)法检测内皮细胞标志蛋白、Smad4蛋白和转化生长因子-β(TGFR-β)/SmAD信号通路相关蛋白的表达。进一步，通过双荧光素酶报告实验、RNA免疫沉淀(RIP)实验和生物素标记的RNA下拉实验证实miR-486-5p与NEAT1或Smad4的关系。在后囊混浊和转化生长因子-β-2诱导的晶状体上皮细胞中，NEAT1表达上调，miR-486-5p表达下调。NEAT1可逆转转化生长因子-β-2对晶状体上皮细胞增殖、迁移、侵袭和上皮转化的促进作用。MIR-486-5P可被NEAT1海绵吞噬，其抑制剂可逆转NEAT1沉默对转化生长因子-β2诱导的晶状体上皮细胞生长的抑制作用。Smad4作为miR-486-5p的靶点，其过表达恢复了miR-486-5p过表达对转化生长因子-β2诱导的晶状体上皮细胞生长的抑制作用。转化生长因子-β/Smad4信号通路的活性受NET1/miR-486-5p/Smad4轴的调控。我们的研究表明，NEAT1在PCO的进展中具有积极的作用，有望成为PCO治疗的新靶点。
Abnormal proliferation, metastasis and epithelial-mesenchymal transformation (EMT) of lens epithelial cells (LECs) are direct factors of posterior capsular opacification (PCO). Nuclear enriched abundant transcript 1 (NEAT1) has been shown to promote cell proliferation, metastasis and EMT, but whether it affects the progression of PCO is unclear. The expression of NEAT1, microRNA-486-5p (miR-486-5p) and Drosophila mothers against decapentaplegic 4 (SMAD4) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation of cells was measured via 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Transwell assay was employed to detect the migration and invasion of cells. The levels of EMT marker proteins, SMAD4 protein and transforming growth factor-β (TGF-β)/SMAD signaling pathway-related proteins were assessed by western blot (WB) analysis. Further, the relationship between miR-486-5p and NEAT1 or SMAD4 was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and biotin-labeled RNA pull-down assay. NEAT1 is upregulated and miR-486-5p is downregulated in the posterior capsular tissues of PCO patients and TGF-β2-induced LECs. Interference of NEAT1 reverses the promoting effect of TGF-β2 on the proliferation, migration, invasion and EMT of LECs. MiR-486-5p can be sponged by NEAT1, and its inhibitor reverses the suppression effect of NEAT1 silencing on the progression of TGF-β2-induced LECs. SMAD4 functions as a target of miR-486-5p, and its overexpression recovers the inhibition effect of miR-486-5p overexpression on the progression of TGF-β2-induced LECs. The activity of the TGF-β/SMAD signaling pathway is regulated by the NEAT1/miR-486-5p/SMAD4 axis. Our study shows that NEAT1 has a positive effect on the progression of PCO and is expected to become a new target for PCO treatment.
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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：
6.6
作者：
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DOI：
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发表时间：
2017-01-01
期刊：
LONG NON CODING RNA BIOLOGY
影响因子：
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作者：
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作者：
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