IGF2-aerived miR-483-3p contributes to macrosomia through regulating trophoblast proliferation by targeting RB1CC1
IGF2-aerived miR-483-3p contributes to macrosomia through regulating trophoblast proliferation by targeting RB1CC1
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IGF2 衍生的 miR-483-3p 通过靶向 RB1CC1 调节滋养层增殖，从而促进巨大儿
DOI：
10.1093/molehr/gay027
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发表时间：
2018-09-01
影响因子：
4
通讯作者：
Wu, Wei
中科院分区：
文献类型：
--
作者：
Li, Jing;Fu, Ziqiang;Wu, Wei
研究问题：胰岛素样生长因子2（IGF2）衍生的miR-483 - 3p在巨大儿中的作用是什么？总结回答：IGF2衍生的内含子miR-483 - 3p在巨大儿胎盘中过表达，miR-483 - 3p通过下调其靶点RBI诱导卷曲螺旋1（RB1CC1）促进HTR-8/SVneo绒毛外滋养层细胞系增殖。据报道，巨大儿的发生可归因于胎盘细胞的过度增殖。microRNAs（miRNAs）通过调控其靶基因在胎儿和胎盘的发育过程中发挥重要作用。在这里，我们研究了IGF2衍生的内含子miR-483 - 3p在巨大儿中的作用。研究设计、规模、持续时间：将30名巨大儿孕妇胎盘组织中IGF2、miR-483 - 3p及其靶基因的表达与30名妊娠匹配的健康孕妇对照进行比较。在体外研究中，人早孕绒毛外滋养层细胞系，HTR-8/SVneo cells被使用。参与者/材料，设置，方法：胎盘组织收集自患有巨大儿的孕妇，无糖尿病或其他并发症（n = 30）和健康孕妇对照组（n = 30）。用特异性miRNA模拟物或抑制剂转染HTR-8/SVneo细胞。通过定量实时PCR测量从胎盘组织或细胞分离的miRNA和mRNA。通过蛋白质印迹法测量蛋白质。使用比色增殖测定法测定细胞增殖。流式细胞仪分析细胞周期和凋亡情况。使用TargetScan、miRanda、miRDB和DIANA算法预测miR-483 - 3p的推定靶标。采用双荧光素酶报告基因检测miR-483 - 3p与RB1CC 1的相关性。主要结果及机会作用：巨大儿胎盘组织中IGF 2源性miR-483 - 3p高表达。miR-483 - 3p促进HTR-8/SVneo细胞增殖，并与宿主基因IGF 2呈正相关。随后，RB1CC1被证实是miR-483 - 3p的直接靶点，可能是miR-483 - 3p调节细胞生长的重要介质。大规模数据：N/A。局限性，预防原因：未研究这些参与者血清中IGF 2及其内含子miR-483 - 3p的水平。需要进一步的研究来了解巨大儿IGF2和miR-483 - 3p增加的原因的机制，这些发现的更广泛的意义：这些发现提供了一个新的见解内含子miRNA及其宿主基因在巨大儿的发展中的作用。此外，它可能为巨大儿的预后和治疗干预提供一个新的靶点。
STUDY QUESTION: What is the role of insulin-like growth factor 2 (IGF2)-derived miR-483-3p in macrosomia?SUMMARY ANSWER: IGF2-derived intronic miR-483-3p is overexpressed in macrosomia placentas, and miR-483-3p prompts HTR-8/SVneo extravillous trophoblast cell line proliferation through down-regulation of its target RBI inducible coiled-coil 1 (RB1CC1).WHAT IS KNOWN ALREADY: Macrosomia is a common pregnancy-associated disease and causes a number of adverse maternal and perinatal outcomes. The development of macrosomia is reportedly attributable to over proliferation of the placental cells. MicroRNAs (miRNAs) play an important role in the development of fetal and placenta by regulating their target genes. Here, we investigated the role of IGF2-derived intronic miR-483-3p in macrosomia.STUDY DESIGN, SIZE, DURATION: The expression of IGF2, miR-483-3p and its target gene in placental tissues from 30 pregnant women who had macrosomia was compared to those of 30 gestation-matched healthy pregnant controls. For in vitro studies, the human first trimester extravillous trophoblast cell line, HTR-8/SVneo cell was used.PARTICIPANTS/MATERIALS, SETTING, METHODS: Placenta tissues were collected from pregnant women who had macrosomia without diabetes or other complications (n = 30) and healthy pregnant controls (n = 30). HTR-8/SVneo cells were transfected with specific miRNA mimics or inhibitors. MiRNA and mRNA isolated from placenta tissues or cells were measured by quantitative real-time PCR. Protein was measured by western blot. Cell proliferation was assayed using a colorimetric proliferation assay method. Cell cycle and apoptosis were analyzed by flow cytometry. The putative targets of miR-483-3p were predicted using the TargetScan, miRanda, miRDB and DIANA algorithms. Dual luciferase reporter assay was used to measure the relationship of miR-483-3p and RB1CC1.MAIN RESULTS AND THE ROLE OF CHANCE: IGF2-derived miR-483-3p was overexpressed in macrosomia placentas. miR-483-3p promoted proliferation in HTR-8/SVneo cells and had a positive relationship with its host gene IGF2. Subsequently, RB1CC1 was confirmed as a direct target of miR-483-3p, which may be an important mediator of cell growth regulation for miR-483-3p.LARGE SCALE DATA: N/A.LIMITATIONS, REASONS FOR CAUTION: The level of IGF2 and its intronic miR-483-3p in the serum of these participants was not investigated. Further studies are required to understand the mechanisms underlying the cause of the increase of IGF2 and miR-483-3p in macrosomia.WIDER IMPLICATIONS OF THE FINDINGS: These findings give a new insight into the role of intronic miRNA and its host gene in the development of macrosomia. Furthermore, it may offer a new target for prognostic and therapeutic intervention for macrosomia.