OBJECTIVE: MicroRNA (miRNAs) are single stranded, small non-coding RNAs that regulate gene expression. Because they are stable in serum, they are being developed as biomarkers for cancer and other diseases. In MS, miRNAs have been studied in cell populations but not in the circulation. In MS a major challenge is to develop immune biomarkers to monitor disease. We asked if circulating miRNAs could be identified in MS and whether they linked to disease stage and/or disability.
METHODS: 368 miRNAs were measured in EDTA plasma in 10 RRMS, 9 SPMS and 9 healthy controls (HC) using qPCR and Exiqon Human Panel I assays. 19 miRNAs from this discovery set were validated using qPCR on an independent set of 50 RRMS, 51 SPMS and 32 HCs.
RESULTS: We found that circulating miRNAs are differentially expressed in RRMS and SPMS vs. HC and in RRMS vs. SPMS. We also found miRNAs linked to EDSS. hsa-miR-92a-1* was identified in the largest number of comparisons. It was different in RRMS vs. SPMS, RRMS vs. HC and showed association with EDSS and disease duration. miR-92 has target genes involved in cell cycle regulation and cell signaling. The let-7 family of miRNAs differentiated SPMS vs. HC and RRMS vs. SPMS. Let-7 miRNAs regulate stem cell differentiation, T cell activation, activate TLR-7 and are linked to neurodegeneration. hsa-miR-454 differentiated RRMS vs. SPMS and hsa-miR-145 differentiated RRMS vs. HC and RRMS vs. SPMS; both were associated with EDSS. Interestingly, the same circulating miRNAs (let-7 and miR-92) that were differentially expressed in RRMS vs. SPMS also differentiated ALS vs. RRMS subjects, but were not different between SPMS and ALS, suggesting similar processes may occur in SPMS and ALS.
INTERPRETATION: Our results establish circulating miRNAs as a readily accessible blood biomarker to monitor disease in MS.
We have a number of posts on microRNA, which are part of the epigentic control of gene function. This means they act to influence how much of the gene product is made and where and when. There are hundreds of microRNA called Mir in the human body. This study looks for Mir in the blood and find there are changes in Mir92 but this Mir92 has been implicated to reflect changes in other diseases too. so what this means for MS is not clear. Mir-145 apparently distinguished RRMS from SPMS but what we want to know is what markers predict change before it happens. For biomarkers to be useful they need to reflect/detect some form of specific process. This no doubt adds to the MS jigsaw puzzle but will it provide something useful?