مقالات پذیرفته شده در هفتمین کنگره بین المللی زیست پزشکی
Downregulation of PCAT-1 long non-coding RNA in children with autism spectrum disorder
Downregulation of PCAT-1 long non-coding RNA in children with autism spectrum disorder
Vera Ebrahimi,1Zeinab Shirvani-Farsani,2Mehdi Safaeizadeh,3,*
1. Department of Cell and Molecular Biology, Faculty of Life Sciences and Technology, Shahid Beheshti University, Tehran, Iran 2. Department of Cell and Molecular Biology, Faculty of Life Sciences and Technology, Shahid Beheshti University, Tehran, Iran 3. Department of Plant Biotechnology, Faculty of Life Sciences and Technology, Shahid Beheshti University, Tehran, Iran
Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental childhood-onset disorder that can continue life-long. This disorder affects socio-communicative development and also causes rigidity and ritualistic/repetitive patterns of behavior. The prevalence of ASD is approximately 1 percent with a ratio of 4:1 in male to female. The etiological architecture of ASD is complex. Genetic and epigenetic factors play a crucial role in the pathogenesis of ASD and it has been estimated that up to 1000 genetic loci are potentially implicated in ASD. One of the factors involved in ASD is long noncoding RNAs. Although researchers have not yet understood the functions of lncRNAs in this disorder, there are several studies that have reported dysregulated expression of lncRNAs in correlation with the pathogenesis of ASD. In the current research, we evaluated the expression level of lncRNA, namely PCAT-1 in the peripheral blood of patients with ASD and healthy subjects.
Methods: This study was performed using peripheral blood samples of 71 children. The age range was from 4 to 15 years old. 30 children were diagnosed with ASD and 41 of them were healthy children. RNA extraction and cDNA synthesis were done on each blood sample. Forward and reverse primers were designed specifically for PCAT-1 lncRNA. For evaluation of expression levels of PCAT-1, Real-Time PCR was performed. Finally, Graph Pad Prism6 software was used for statistical analysis
Results: Our study showed that there is a significant difference between the amount of expression of PCAT-1 in children with ASD and healthy children (P value <0.0001). According to our investigations expression of PCAT-1 in ASD patients was 40 times lower than the healthy population. Specificity and sensitivity of PCAT-1 expression levels were investigated, using ROC Curve analysis; the results showed 0.843 erea under the curve (AUC), P value <0.0001, sensitivity =80%, specificity =70.73%, and cut off >6.067. These results can propose the potential of using PCAT-1 as a diagnostic biomarker for ASD. In brief, our investigations showed that PCAT-1 expression levels in ASD patients were meaningfully downregulated in comparison with healthy children.
Conclusion: This study can provide clues for an association between reduced levels of PCAT-1 and ASD, as well as the possibility of using PCAT-1 as a diagnostic biomarker for ASD. Given that ASD patients generally are being diagnosed by behavioral symptoms such as social communications and interactions and up to now, there are no significant lab-based examinations to diagnose these cases; using long non-coding RNAs such as PCAT-1 as diagnostic biomarkers could be a milestone in diagnosis of ASD. Also because of the overlapping of some symptoms of ASD with combined psychiatric conditions, the possibility of false diagnoses is inevitable; but in the case of using PCA-1 expression as a biomarker, the chances of accurate diagnosis will elevate. Due to the limitations of this study, complementary investigations are needed to prove our findings and demonstrate the role of PCAT-1 in the pathobiology of ASD.