Profiling of Circulating Serum MicroRNAs in Children with Autism Spectrum Disorder using Stem-loop qRT-PCR Assay.

BACKGROUND: Development of biomarkers for autism spectrum disorder (ASD) has still remained a challenge to date. Recently, alterations of the expression of microRNAs (miRNAs) in peripheral blood, serum and post-mortem brain tissue have been linked to ASD. miRNAs are known to be secreted by various cell types and can mediate transmission of information into recipient cells and to modulate their physiological functions. On this basis it is assumed that circulating miRNAs could be useful biomarkers for the diagnosis or prognosis of pathological conditions. AIM: The aim of this study was to test whether circulating miRNAs display differential expression profile in serum of ASD patients. PATIENTS AND METHODS: The relative expression levels of 42 miRNAs were analyzed by stem-loop qRT-PCR assay in the serum of ASD patients compared to healthy controls. RESULTS: The results indicated that 11 miRNAs in ASD patients were substantially higher expressed than these in control subjects, and 29 miRNAs were lower expressed, respectively. In addition, target gene analysis displayed that the altered serum miRNAs targeted some important genes like alpha 1C subunit of voltage-dependent calcium channel, L type, (CACNA1C), beta 1 subunit of voltage-dependent calcium channel (CACNB1) and other genes involved in epigenetic processes like dicer 1, coding ribonuclease type III (DICER). CONCLUSION: Our results suggested that differentially expressed miRNAs in serum might be involved in ASD molecular pathways, and serum miR-424-5p, miR-197- 5p, miR-328-3p, miR-500a-5p, miR-619-5p, miR-3135a, miR-664a-3p, and miR- 365a-3p might be able to serve as potential biomarkers for ASD because they displayed significant alterations in the expression profile in children diagnosed with ASD.

Circulating microRNAs as a Novel Class of Potential Diagnostic Biomarkers in Neuropsychiatric Disorders.

Neuropsychiatric diseases, such as schizophrenia, bipolar disorder (BD), major depressive disorder (MDD) and autism spectrum disorder (ASD), are a huge burden on society, impairing the health of those affected, as well as their ability to learn and work. Biomarkers that reflect the dysregulations linked to neuropsychiatric diseases may potentially assist the diagnosis of these disorders. Most of these biomarkers are found in the brain tissue, which is not easily accessible. This is the challenge for the search of novel biomarkers that are present in various body fluids, including serum or plasma. As a group of important endogenous small noncoding RNAs that regulate gene expression at post-transcriptional level, microRNAs (miRNAs) play a crucial role in many physiological and pathological processes. Previously, researchers discovered that miRNAs contribute to the neurodevelopment and maturation, including neurite outgrowth, dendritogenesis and dendritic spine formation. These developments underline the significance of miRNAs as potential biomarkers for diagnosing and prognosing central nervous system diseases. Accumulated evidence indicates that there are considerable differences between the cell-free miRNA expression profiles of healthy subjects and those of patients. Therefore, circulating miRNAs are likely to become a new class of noninvasive, sensitive biomarkers. Despite the fact that little is known about the origin and functions of circulating miRNAs, their essential roles in the clinical diagnosis and prognosis of neuropsychiatric diseases make them attractive biomarkers. In this review we cover the increasing amounts of dataset that have accumulated in the last years on the use of circulating miRNAs and their values as potential biomarkers in most areas of neuropsychiatric diseases.