Humira treatment restores dysregulated lncRNA gene networks

from Psoriasis News Today by Joana Fernandes –

Researchers identified abnormal genetic pathways associated with psoriasis, some of which may be restored after treatment with Humira (adalimumab), according to a new study published in the journal BMC Genomics.

In the study, “Network Analysis Of Psoriasis Reveals Biological Pathways And Roles For Coding And Long Non-Coding RNAs,” researchers observed that many pathways associated with psoriasis included long non-coding RNAs (lncRNA), a group of molecules produced within cells that are believed to, among other functions, control the expression of certain genes.

The study aimed to understand exactly what pathways are differently activated between psoriatic and healthy skin. To do so, researchers analyzed gene expression in skin samples from 18 psoriasis patients (before and after treatment with the TNF-α inhibitor Humira) and 16 healthy controls.

The comparison revealed three genetic network modules that were significantly correlated with psoriasis, and six network modules that were significantly correlated with biologic treatment. Psoriasis was mainly associated with expression changes in genes involved in the metabolism of fats and olfactory signaling. Treatment was associated with changes in genes related with the immune system and cell death.

“We discovered that the majority of the top significantly associated modules were composed of lncRNAs, with 90 % of the top 10 [psoriasis versus control] modules consisting of at least 80 % lncRNAs, and 70 % of the top 10 [psoriaris versus treatment] modules consisting of at least 70 % lncRNAs. This suggests that lncRNAs likely play a significant role in the regulation of critical pathways in the pathogenesis of psoriasis.”

Importantly, the dysregulated gene networks were restored to pre-psoriatic baseline levels after treatment with Humira.

“We believe that future studies of populations of isolated individual cell types … and single-cell approaches will allow researchers to precisely match each gene network to a particular cell type, shedding further light on which cells are triggering psoriasis and which cells may be conferring resistance to currently available therapies,” the researchers wrote. “This matching of gene networks to cell type (and subcell type) may also aid in functional analyses of lncRNAs, a vast majority of which have no known function.”

Intramodular analysis reveals hub genes in the top correlated module in PPvNN


Graphical illustration of intramodular analysis starting with identification of the most correlated modules and plotting MM against GS for the top correlated modules a. After hub genes are identified, a network plot of these genes is produced b. In this case, the network plot is of the hub genes of the PPvNN blue module. The relative size of each hub indicates the degree of connectivity (number of edges) for each gene

Source – Psoriasis News Today

Ahn R, Gupta R, Lai K, Chopra N, Arron ST, Liao W. (2016) Network analysis of psoriasis reveals biological pathways and roles for coding and long non-coding RNAs. BMC Genomics 17(1):841. [article]

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