Abstract
Autism spectrum disorder (ASD) is a long-standing neurodevelopmental condition with prominent effects on social behavior of affected children. This disorder has been linked with neuroinflammatory responses. NF-κB has been shown to affect these responses in the orbitofrontal cortex of patients with ASD, thus being implicated in the pathogenesis of ASD. We measured expression of some NF-κB-associated lncRNAs and mRNAs (DILC, ANRIL, PACER, CHAST, ADINR, DICER1-AS1, HNF1A-AS1, NKILA, ATG5 and CEBPA) in the peripheral blood of ASD kids vs. healthy children. Expression quantities of ADINR, ANRIL, DILC, NKILA and CHAST were meaningfully higher in ASD cases compared with healthy kids (Posterior Beta = 1.402, P value < 0.0001; Posterior Beta = 2.959, P value < 0.0001; Posterior Beta = 0.882, P value = 0.012; Posterior Beta = 1.461, P value < 0.0001; Posterior Beta = 0.541, P value = 0.043, respectively). The Bonferroni corrected P values for these lncRNAs remained significant except for CHAST and DILC. Expression levels of other genes were not considerably different between cases and controls. Expressions of ATG5, DICER-AS1 and DILC were correlated with age of ASD patients (P < 0.0001). Among ASD cases, the most robust correlation has been detected between ADINR and NKILA (r = 0.87, P < 0.0001). Expression of none of genes has been correlated with age of healthy children. Among this group of children, expression levels of ADINR and CHAST were robustly correlated (r = 0.83, P < 0.0001). ANRIL had the greatest AUC value (AUC = 0.857), thus the best diagnostic power among the assessed genes. NKILA ranked the second position in this regard (AUC = 0.757). Thus, NF-κB-associated lncRNAs might partake in the pathogenesis of ASD.
Highlights
Autism spectrum disorder (ASD) is a long-standing neurodevelopmental condition pigeonholed by defects in social abilities and speaking communication and the occurrence of stereotypic behaviors and interests (American Psychiatric Association, 2013)
Expression quantities of ADINR, ANRIL, DILC, NKILA and CHAST were meaningfully higher in ASD cases compared with healthy kids (Posterior Beta = 1.402, P value < 0.0001; Posterior Beta = 2.959, P value < 0.0001; Posterior Beta = 0.882, P value = 0.012; Posterior Beta = 1.461, P value < 0.0001; Posterior Beta = 0.541, P value = 0.043, respectively)
Based on our recent experience in patients with schizophrenia regarding the possible role of Nuclear factor κ-lightchain-enhancer of activated B cells (NF-κB)-related genes, we hypothesized that these genes might be involved in ASD
Summary
Autism spectrum disorder (ASD) is a long-standing neurodevelopmental condition pigeonholed by defects in social abilities and speaking communication and the occurrence of stereotypic behaviors and interests (American Psychiatric Association, 2013). Nuclear factor κ-lightchain-enhancer of activated B cells (NF-κB) has been shown to regulate response to extracellular stress and expression amounts of pro-inflammatory cytokines (Pahl, 1999; Perkins, 2004). A previous study has reported aberrant levels of NF-κB in orbitofrontal cortex of patients with ASD especially in extremely activated microglia and its role in the molecular cascade resulting in the neuroinflammation, in inhabitant immune cells in brain areas linked with the behavioral changes in ASD (Young et al, 2011). LncRNAs are a group of regulatory transcripts with sizes more than 200 nt to several kbs These transcripts have influential effects on expression of genes through modulating chromatin structure, serving as enhancers for transcription, serving as molecular decoys to limit availability of other regulatory molecules and making scaf-folds for recruitment of other biomolecules (Fang and Fullwood, 2016). A bulk of evidence has shown particular involvement of these transcripts in the pathoetiology of neurodevelopmental diseases (Roberts et al, 2014)
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