Post-traumatic stress disorder (
PTSD), which frequently occurs in the aftermath of a psychologically traumatic event is characterized by heightened
inflammation. People with
PTSD also suffer from a number of comorbid clinical and behavioral disorders that are related to chronic
inflammation. Thus, understanding the mechanisms of enhanced
inflammation in
PTSD can provide insights into the relationship between
PTSD and associated comorbid disorders. In the current study, we investigated the role of large intervening non-coding RNAs (
lincRNAs) in the regulation of
inflammation in people diagnosed with
PTSD. We observed that WNT
ligand, WNT10B, was upregulated in the peripheral blood mononuclear cells (PBMCs) of
PTSD patients. This observation was associated with higher
H3K4me3 signals around WNT10B promotor in
PTSD patients compared to those without
PTSD. Increased
H3K4me3 resulted from LINC00926, which we found to be upregulated in the
PTSD sample, bringing in
histone methyltransferase, MLL1, onto WNT10B promotor leading to the introduction of H3K4 trimethylation. The addition of recombinant human WNT10B to pre-activated peripheral blood mononuclear cells (PBMCs) led to increased expression of inflammatory genes such as IFNG and IL17A, suggesting that WNT10B is involved in their upregulation. Together, our data suggested that LINC00926 interacts physically with MLL1 and thereby controls the expression of IFNG and IL17A. This is the first time a
long non-coding RNA is shown to regulate the expression of WNT10B and consequently
inflammation. This observation has high relevance to our understanding of disease mechanisms of
PTSD and comorbidities associated with
PTSD.