4.5 Article

MEG3 lncRNA is over-expressed in autism spectrum disorder

Journal

METABOLIC BRAIN DISEASE
Volume 36, Issue 8, Pages 2235-2242

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11011-021-00764-x

Keywords

Autism spectrum disorder; MEG3; GAS5; CYTOR; UCA1; CRYBG3

Funding

  1. Shahid Beheshti University of Medical Sciences

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The study revealed a significant upregulation of MEG3 expression in children with ASD, while the expression levels of other lncRNAs and the CRYBG3 gene showed no significant differences. Strong correlations were found among GAS5/CYTOR, CYTOR/UCA1, and GAS5/UCA1 in children with ASD.
Long non-coding RNAs (lncRNAs) comprise a group of regulatory transcripts which partake in the biological processes leading to development of neuropsychiatric disorders such as autism spectrum disorder (ASD). We measured circulatory levels of MEG3, GAS5, CYTOR, UCA1 lncRNAs and CRYBG3 gene in children with ASD and controls. Expression of MEG3 was remarkably higher in children with ASD when compared with controls (Posterior Beta = 2.919, SE = 0.51, P value < 0.0001). This difference was significant among male subgroups (Posterior Beta = 2.913, SE = 0.56, P value < 0.0001) as well as female subgroups (95% CrI for Beta = [0.29, 2.4], SE = 0.53, P value < 0.0001). Expression levels of other lncRNAs or CRYBG3 were not different between children with ASD and controls. Among children with ASD, the most robust correlations were found between GAS5/CYTOR, CYTOR/UCA1 and GAS5/UCA1 with correlation coefficients of 0.83, 0.83 and 0.73, respectively. Among controls, GAS5/UCA1, MEG3/UCA1 and GAS5/MEG3 pairs had the highest correlation coefficients (0.89, 0.84 and 0.80, respectively). ROC curve analysis revealed that MEG3 can distinguish children with ASD from controls with diagnostic power of 0.792 (P value < 0.0001). This value was higher among male subgroups (AUC = 0.84, P value < 0.0001) compared with female subgroups (AUC = 0.727, P value = 0.0727). The current research highlights the role of MEG3 in ASD and provides clues for depiction of an lncRNA network with possible contribution in the pathogenesis of ASD.

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