Altered expression of CCAT1 and CCAT2 lncRNAs in autism spectrum disorder

Abstract

Long non-coding RNAs (lncRNAs) have been proposed as important contributors in the development of brain and in the pathobiology of neurodevelopmental disorders. Altered levels of a number of lncRNAs in the circulation have been linked with the pathogenesis of autism spectrum disorder (ASD). We measured expression of Colon Cancer Associated Transcripts 1 and 2 (CCAT1 and CCAT2) in the circulation of ASD cases and healthy children. Expression of CCAT1 was remarkably lower in ASD children than in healthy children (Posterior Beta = −0.682, SE = 0.35, adjusted P value = 0.022). Conversely, expression of CCAT2 was higher in ASD cases compared with controls (Posterior Beta = 2.237, standard error (SE) = 0.38, adjusted P value<0.0001). Subsequently, we compared expressions of CCAT1 and CCAT2 between males and females demonstrating no substantial difference in their expression between these two groups (P values = 0.209 and 0.231, respectively). The interaction between group and gender was insignificant for both lncRNAs (P values = 0.951 and 0.482, respectively). While CCAT1 expression was not different among age-based subgroups, CCAT2 expression was significantly lower in healthy children age between 5 and 6 years compared with the other groups of healthy children. CCAT1 could differentiate between these two groups with area under curve (AUC) = 0.663, P value = 0.016, sensitivity = 54.33% and specificity = 82.93%. Diagnostic power of CCAT2 was superior to CCAT1 as revealed by AUC = 0.779, P value<0.0001, sensitivity = 86.67% and specificity = 73.17%. Taken together, CCAT1 and CCAT2 are suggested as candidate for functional studies in ASD.