Tissue and circulating microRNA co-expression analysis reveals potential involvement of miRNAs in the pathobiology of frontal fibrosing alopecia (FFA). Tziotzios C, Ainali C, Holmes S et al. JID (2017), doi: 10. 1016/j.jid.2017.06.030
MicroRNAs (miRNAs) are small, non coding RNAs that may impact protean biologic functions. This study sought to characterise miRNAs in FFA and probe disease relevance by undertaking tissue and circulating miRNA co-expression analysis in FFA cases and matched controls.
They recruited seven newly diagnosed, treatment-naive FFA cases and 7 matched controls. Temporal scalp skin biopsies were obtained from all cases and controls for microarray analysis. Venous blood samples were also obtained from a separate cohort of 10 biopsy-proven, treatment naive FFA cases and 10 matched controls for circulating miRNA analysis. They constructed a co-expression network of tissue miRNAs by assessing pairwise similarity of miRNAs expressed in each group of cases and controls, calculated using the Pearson correlation coefficient (PCC). The resulting FFA network displayed 2,089 co-expressed miRNAs (nodes) with 3,009 non-duplicate interactions (edges), while for controls there were 2,100 co-expressed miRNAs (nodes) with 2,934 non-duplicate interactions (edges).
For the circulating miRNA dataset, 55 miRNAs were upregulated in FFA while 11 miRNAs were downregulated compared to controls. To further evaluate differentially expressed circulating miRNAs, they were mapped within tissue-specific co-expression networks. There were 17 miRNAs common in both networks (cases and controls): 3 of these were specific to controls while 9 were representative of FFA. Of those 9 circulating miRNAs, 4 were found to be highly predictive of disease status: hsa-let-7d-5p, hsa-miR-18a-5p, has-miR-20a-5p, and hsa-miR-19a-3p. Finally, they applied GAGE analysis and found MAPK signalling, endocytosis and focal adhesion pathways to be down regulated and enriched in the networks of co-targeting genes across these 4 miRNAs. The authors concluded that these 4 circulating miRNAs were highly predictive of disease status in FFA but that further studies are required to determine mechanistic relevance.
By Nicola Cooke