LncRNA-SULT1C2A regulates Foxo4 in congenital scoliosis by targeting rno-miR-466c-5p through PI3K-ATK signalling
LncRNA-SULT1C2A regulates Foxo4 in congenital scoliosis by targeting rno-miR-466c-5p through PI3K-ATK signalling
复制标题
LncRNA-SULT1C2A 通过 PI3K-ATK 信号传导靶向 rno-miR-466c-5p，调节先天性脊柱侧凸中的 Foxo4
DOI：
10.1111/jcmm.14355
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发表时间：
2019-07-01
影响因子：
5.3
通讯作者：
Shen, Jianxiong
中科院分区：
文献类型：
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作者：
Chen, Chong;Tan, Haining;Shen, Jianxiong
先天性脊柱侧凸（congenitalscoliosis，CS）是脊椎发育异常的结果，但其发病机制尚不清楚。长链非编码RNA（lncRNA）与胚胎发育有关，但它们在CS中的作用仍不清楚。在这项研究中，我们研究了一个特定的lncRNA，SULT 1C 2A，在维生素A缺乏（VAD）诱导的CS大鼠模型的体节发生的作用和机制。生物信息学分析和实时荧光定量PCR（qRT-PCR）结果显示，VAD组SULT 1C 2A表达下调，同时伴有mno-miR-466 c-5 p表达增加，而Foxo 4和体细胞发生相关基因Pax 1、Nkx 3 -2和Sox 9表达降低。荧光素酶报告基因和小干扰RNA（siRNA）分析显示，SULT 1C 2A作为竞争性内源RNA通过直接结合抑制rno-miR-466 c-5 p表达，而rno-miR-466 c-5 p通过结合其3'非翻译区（UTR）抑制Foxo 4表达。如通过qRT-PCR和北方印迹分析检测到的，SULT 1C 2A、rno-miR-466 c-5 p和Foxo 4轴的时空表达在GD 3、8、11、15和21上动态改变，蛋白激酶B（AKT）磷酸化和PI 3 K表达具有平行变化。综上所述，我们的发现表明，SULT 1C 2A通过在VAD-CS大鼠模型中经由PI 3 K-ATK信号传导途径负性调节rno-miR-466 c-5 p表达来增强Foxo 4表达。因此，SULT 1C 2A可能是治疗CS的潜在靶点。
Congenital scoliosis (CS) is the result of anomalous vertebrae development, but the pathogenesis of CS remains unclear. Long non-coding RNAs (lncRNAs) have been implicated in embryo development, but their role in CS remains unknown. In this study, we investigated the role and mechanisms of a specific lncRNA, SULT1C2A, in somitogenesis in a rat model of vitamin A deficiency (VAD)-induced CS. Bioinformatics analysis and quantitative real-time PCR (qRT-PCR) indicated that SULT1C2A expression was down-regulated in VAD group, accompanied by increased expression of rno-miR-466c-5p but decreased expression of Foxo4 and somitogenesis-related genes such as Pax1, Nkx3-2 and Sox9 on gestational day (GD) 9. Luciferase reporter and small interfering RNA (siRNA) assays showed that SULT1C2A functioned as a competing endogenous RNA to inhibit rno-miR-466c-5p expression by direct binding, and rno-miR-466c-5p inhibited Foxo4 expression by binding to its 3' untranslated region (UTR). The spatiotemporal expression of SULT1C2A, rno-miR-466c-5p and Foxo4 axis was dynamically altered on GDs 3, 8, 11, 15 and 21 as detected by qRT-PCR and northern blot analyses, with parallel changes in Protein kinase B (AKT) phosphorylation and PI3K expression. Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno-miR-466c-5p expression via the PI3K-ATK signalling pathway in the rat model of VAD-CS. Thus, SULT1C2A may be a potential target for treating CS.