Figure 4

Levels of TDP-43 binding miRNAs in LCLs of healthy controls and ALS patients. Genetic backgrounds of the LCLs are indicated by the name of the proteins carrying the mutation, by C9orf72 for LCLs with a hexanucleotide expansion in C9ORF72 or by SALS for LCLs from sporadic ALS patients with no mutation in known ALS genes. MiRNAs were measured by qPCR and normalized to U6 snRNA. Indicated is the expression of respective miRNAs relative to mean values of the control group. (A) Both strands of miR-143 are downregulated in LCLs of all ALS patients tested irrespective of the genetic status. The lack of statistical significance of the decrease of miR-143-3p in SOD1 and TARDBP mutant LCLs is rather due to the small sample number available than to indistinct results. Though, both show a strong trend (p ≤ 0.11). (B) Both strands of miR-574 and, even more pronounced, of miR-132 are reduced in TARDBP, FUS and C9ORF72 mutant LCLs as well as in LCLs derived from SALS patients. In contrary, none of these four miRNAs is altered in SOD1 mutant LCLs paralleling TDP-43 and FUS pathology. Also here, lack of statistical significance for both strands of miR-574 in TARDBP mutant LCLs is due to a small sample number available and results showed a strong trend (p ≤ 0.09). (C) While miR-558-3p is unaffected throughout all ALS groups, miR-663a and miR-9-5p are exclusively downregulated in FUS mutant LCLs. Let-7b levels are significantly reduced in both FUS and C9ORF72 mutant LCLs (bars indicate mean ± S.E.M.; n = 3–8).