Chinese Han Patients With Congenital Scoliosis And Normal Serum Micrornas Contrast Research

BackgroundCongenital scoliosis is a lateral curvature of the spine caused by vertebral anomalies that result in an imbalance of the longitudinal growth of the spine. The congenital scoliosis could be divided into three types. Type I is failure of formation. Type Ⅱ is failure of segmentation. Type III is a combination of both of these conditions. Congenital anomalies occur in the phase of somitogenesis during embryogenesis. Disruptions in somitogenesis have been shown to result in vertebral malformations. Vertebral defects can arise from the disruption of genes involved in development, drugs, enviromental insults during gestation, or a combination of these factors. Many evidences suggest that CS may be multigenetic disease.MicroRNAs (miRNAs) are classified as regulatory RNAs, and have been proved to play important roles in the development, proliferation and differentiation of various types of cells. It has been reported that miRNA played an important role in the bone development and formation. Recent studies have indicated that miRNA also circulates in serum and plasma. Levels of miRNAs in serum are stable, and consistent among individuals of the same species. For instance, disease-specific serum miRNA has been found in cancer, diabetes, and other diseases.It has been found that both BMD (bone mineral desity) and trabecular bone microsturcture in CS patients were lower than those in normal person, suggesting abnormal bone metabolism in these patients. Until now there has been no study on miRNA in serum of patients with congenital scoliosis.Objectives:1. To detect differential expressed microRNAs in serum between CS and control.2. To analyze the differential expressed microRNAs with bioinformatics analysis.3. To find key microRNA for further research through comparative analysis combined with bioinformatic prediction.Methods1. Serum was collected from3patients with formation failure,3patients with segmentation failure and3age-and gender-matched normal persons. Then total RNA was isolated and tested with Exiqon miRNA Arrays. The slides were scanned and followed by data extraction. After statistical analysis we got the list of differential expressed microRNAs.2. Target gene and pathway prediction was made.3. The key miRNA was selected after comparative analysis combined with bioinformatic prediction.Results1. A list of differential expressed microRNAs was made by setting the hreshold of up/down regulated microRNAs as Foldchange>2and P value<0.05.54up-regulated miRNAs and42down-regulated miRNAs were detected in the segmentation failure group VS control group.19up-regulated miRNAs and28down-regulated miRNAs were detected in formation failure group VS control group. 2. The key miRNAs were selected. For the segmental failure group,11up-regulated:hsa-miR-10a-3p, hsa-miR-10a-5p, hsa-miR-3915, hsa-miR-548j, hsa-miR-378g, hsa-miR-3173-5p, hsa-miR-604, hsa-miR-3913-3p, hsa-miR-4312, hsa-miR-520a-5p and hsa-miR-378c;9down-regulated:hsa-miR-4726-5p, hsa-miR-4472, hsa-miR-181c-5p, hsa-miR-1293, hsa-miR-181d, hsa-miR-138-5p, hsa-miR-144-3p, hsa-miR-30e-3p and hsa-miR-181b-5p. For the formation failure group,5up-regulated:hsa-miR-574-5p, hsa-miR-4796-5p, hsa-miR-548a-5p, hsa-miR-604and hsa-miR-3913-3p;5down-regulated: hsa-miR-4262, hsa-miR-10b-5p, hsa-miR-30e-3p, hsa-miR-4483and hsa-miR-3148.Conclusions1. This is the first time to study comparative serum miRNA of CS. And differential regulated miRNAs in serum were detected between patients and normal persons.2. The key miRNAs of the group of segmentation failure and formation failure were selected for the following research.