Human Blood-Derived lncRNAs in Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder with a significant impact on public health. ASD diagnosis is based on clinical observation and typically occurs around three years of age. The identification of reliable ASD markers could facilitate early diagnosis and help pinpoint therapeutic targets for effective interventions. Long non-coding RNAs (lncRNAs), particularly those derived from blood, have been recently proposed as potential biomarkers in many pathological conditions, including neurological diseases. This manuscript summarizes original studies examining human dysregulated blood-derived lncRNAs as potential ASD biomarkers. LncRNAs are described by grouping them according to the selection strategy used by the authors: (i) lncRNAs involved in biological processes impaired in ASD or in pathological conditions sharing the disrupted signaling pathways of ASD; and (ii) lncRNAs identified through high-throughput analysis. The study highlights key priorities for future research: assessing the ability of lncRNAs to distinguish ASD from other neurological disorders, extending analyses to larger and younger cohorts to validate candidate biomarkers in early life, and integrating multiple data sources to establish validated biomarker networks for clinical application. This review indicates that research on blood-derived lncRNAs in ASD is still in its early stages.

Keywords: ASD; autism spectrum disorder; biomarkers; lncRNA; long non-coding RNA; non-coding RNA; peripheral blood.

Figure 1

Study selection process. The flow diagram shows the number of investigated studies identified (n), according to the declared criteria.

Figure 2

LncRNA-affected molecular mechanism in ASD pathogenesis. A schematic representation of molecular mechanisms observed for MEG3, NEAT1, Shank2-AS, and IFNG-AS1 in ASD cellular and animal models. CDH2, cadherin2; EP300, E1A binding protein p300 transcription factor; YY1, Yin-Yang 1 transcription factor; UBE3A, ubiquitin protein ligase E3A; PI3K/AKT, phosphoinositide 3-kinase/AKT serine/threonine kinase; ⊥ means inhibition; ↓ means promotion; red arrow means increased expression; blue arrow means decreased expression.

Figure 3

LncRNA-affected pathways in ASD pathogenesis. A schematic representation of the main biological pathways affected by dysregulated lncRNAs in ASD.