The role, mechanism and potentially novel biomarker of microRNA-17-92 cluster in macrosomia.

Jing Li,Yankai Xia,Jie Wu Jie Wu,Hua Jiang Hua Jiang,Lou Liu Lou Liu,Daozhen Chen,Wei Wu,Xinru Wang,Hao Gu Hao Gu,Hongjuan Ding Hongjuan Ding,Yali Hu,Liping Chen,Qiuqin Tang Qiuqin Tang

doi:10.1038/srep17212

Abstract

Macrosomia is one of the most common perinatal complications of pregnancy and has life-long health implications for the infant. microRNAs (miRNAs) have been identified to regulate placental development, yet the role of miRNAs in macrosomia remains poorly understood. Here we investigated the role of miR-17-92 cluster in macrosomia. The expression levels of five miRNAs in miR-17-92 cluster were significantly elevated in placentas of macrosomia, which may due to the up-regulation of miRNA-processing enzyme Drosha and Dicer. Cell cycle pathway was identified to be the most relevant pathways regulated by miR-17-92 cluster miRNAs. Importantly, miR-17-92 cluster increased proliferation, attenuated cell apoptosis and accelerated cells entering S phase by targeting SMAD4 and RB1 in HTR8/SVneo cells. Furthermore, we found that expression of miR-17-92 cluster in serum had a high diagnostic sensitivity and specificity for macrosomia (AUC: 80.53%; sensitivity: 82.61%; specificity: 69.57%). Our results suggested that miR-17-92 cluster contribute to macrosomia development by targeting regulators of cell cycle pathway. Our findings not only provide a novel insight into the molecular mechanisms of macrosomia, but also the clinical value of miR-17-92 cluster as a predictive biomarker for macrosomia.

Highlights

Multiple factors have been identified that can affect fetal birth weight, such as genetic factors, various growth factors, hormones, nutrition and placental factors[7]
Our results suggest that expression levels of miR-18a, miR-19a, miR-20a, miR-19b and miR-92a were significantly higher in placentas of macrosomia, and elevated expression of miR-17-92 increased HTR8/ SVneo cells proliferation, attenuated cell apoptosis and accelerated cells entering S phase. miR-17-92 cluster miRNAs contribute to macrosomia development by targeting regulators of cell cycle pathway
The birth weight was significantly higher in neonates with macrosomia than that in normal controls, while pre-pregnant body mass index was significantly lower in group of macrosomia

Summary

Introduction

Multiple factors have been identified that can affect fetal birth weight, such as genetic factors, various growth factors, hormones, nutrition and placental factors[7]. It has been shown that miRNAs are abundantly expressed in placenta, and contribute to regulating placental development[15]. Dysregulated miRNAs expression in placenta have been associated with a variety of pregnancy complications, such as preeclampsia (PE)[16], fetal growth restriction[17], preterm birth[18] and macrosomia[19]. Previous study has shown that miRNAs in miR-17-92 cluster plays play an important role in cell cycle progression, proliferation, apoptosis, invasion and migration[20]. Our results suggest that expression levels of miR-18a, miR-19a, miR-20a, miR-19b and miR-92a were significantly higher in placentas of macrosomia, and elevated expression of miR-17-92 increased HTR8/ SVneo cells proliferation, attenuated cell apoptosis and accelerated cells entering S phase. MiR-17-92 cluster miRNAs contribute to macrosomia development by targeting regulators of cell cycle pathway. MiR-17-92 cluster may be a potential biomarker for the diagnosis of macrosomia

Methods

Results

Conclusion