Table 1.
Summary of miRNAs that are associated with intellectual disabilities.
| MicroRNA | Model/organism | Description | |
|---|---|---|---|
| Target gene/signaling pathway | |||
| miR-155 | DS individuals | Overexpressed in fetal hippocampus and heart samples (Kuhn et al., 2008). | |
| MeCP2 (Keck-Wherley et al., 2011) | |||
| CFH (Li et al., 2012) | Overexpressed in prefrontal cortex samples at all ages studied (from fetus to adulthood) (Kuhn et al., 2010). | ||
| PICALM (Paschou et al., 2012) | Overexpressed in the adult temporal lobe, the spleen, and the liver (Li et al., 2012). | ||
| Ts65Dn mouse model for DS | Overexpressed in the adult hippocampus (Kuhn et al., 2010). | ||
| Overexpressed in adult hippocampus and blood samples (Keck-Wherley et al., 2011). | |||
| Anti-miR treatment restored MeCP2 in adult hippocampus (Kuhn et al., 2010). | |||
| iPSCs generated from human DS amniotic fluid cells | Overexpressed in iPSCs (Lu et al., 2012). | ||
| TNFα-stressed human neuronal-glial cells | Anti-miR treatment restored CFH level (Li et al., 2012). | ||
| Superior temporal neocortex of AD | Overexpressed in neocortical samples (Lukiw and Alexandrov, 2012). | ||
| miR-802 | DS individuals | Overexpressed in fetal hippocampus and heart samples (Kuhn et al., 2008). | |
| MeCP2 (Keck-Wherley et al., 2011) | Overexpressed in prefrontal cortex samples at all ages studied (from fetus to adulthood) (Kuhn et al., 2010). | ||
| Ts65Dn mouse model for DS | Overexpressed in the adult hippocampus (Kuhn et al., 2010). | ||
| Overexpressed in adult hippocampus and blood samples (Keck-Wherley et al., 2011). | |||
| Anti-miR treatment restored MeCP2 in adult hippocampus (Kuhn et al., 2010). | |||
| iPSCs generated from human DS amniotic fluid cells | Overexpressed in iPSCs (Lu et al., 2012). | ||
| miR-199b | Heart failure patients | Overexpressed in biopsies of cardiac tissues (Da Costa Martins et al., 2010). | |
| Dyrk1a (Da Costa Martins et al., 2010) | |||
| SIRT1 (Saunders et al., 2010) | |||
| MHC-CnA mouse | Overexpressed in heart samples (Da Costa Martins et al., 2010). | ||
| Anti-miR treatment restored Dyrk1a level in the heart (Da Costa Martins et al., 2010). | |||
| Mouse embryonic stem cells | Overexpressed miR-199b reduced SIRT1 protein level (Saunders et al., 2010). | ||
| miR-125b | IL-6-stressed NHA | Overexpressed in IL-6-stressed NHA (Pogue et al., 2010). | |
| CDKN2A (Pogue et al., 2010) | Anti-miR treatment restored CDKN2A level (Pogue et al., 2010). | ||
| NR2A and EphA4 (Edbauer et al., 2010) | |||
| Nestin (Cui et al., 2012) | |||
| Hippocampus of newborn | Overexpressed miR-125b reduced Nestin expression and inhibit neural stem/progenitor cells proliferation (Cui et al., 2012). | ||
| Sprague-Dawley rat pups | |||
| E19 rat hippocampal neurons in culture | FMRP was partially depending on miR-125b in suppressing NR2A (Edbauer et al., 2010). | ||
| Overexpressed miR-125b led to longer and thinner dendritic protrusions with reduced synaptic strength (Edbauer et al., 2010). | |||
| miR-125b-2 | DS individuals | Overexpressed in fetal hippocampus and heart samples (Kuhn et al., 2008). | |
| Overexpressed in prefrontal cortex samples at all ages studied (from fetus to adulthood) (Kuhn et al., 2010). | |||
| miR-99a | DS individuals | Overexpressed in fetal hippocampus and heart samples (Kuhn et al., 2008). | |
| TGF-β pathway (Turcatel et al., 2012) | |||
| let-7c | Overexpressed in prefrontal cortex samples at all ages studied (from fetus to adulthood) (Kuhn et al., 2010). | ||
| TLP7 (Lehmann et al., 2012) | |||
| iPSCs generated from human DS amniotic fluid cells | Overexpressed in iPSCs (Lu et al., 2012). | ||
| miR-214 | Ts65Dn mouse model for DS | Overexpressed in adult hippocampus samples (Keck-Wherley et al., 2011). | |
| CTTNBP2 and ANK2 (Paschou et al., 2012) | |||
| Ncx1 (Aurora et al., 2012) | |||
| miR-214 KO mouse | Increased NCX1 protein in heart samples (Aurora et al., 2012). | ||
| miR-223 | Ts65Dn mouse model for DS | Overexpressed in adult hippocampus and blood samples (Keck-Wherley et al., 2011). | |
| GluR2 and NR2B (Harraz et al., 2012) | |||
| XLID individuals | Mutation found in pre-miRNA sequence (Chen et al., 2007). | ||
| P15–P20 miR-223 KO mouse hippocampal neurons | Increased GluR2 and NR2B protein levels, and promoted NMDA-induced calcium influx (Harraz et al., 2012). | ||
| P15–P20 miR-223 WT mouse hippocampal neurons | Overexpressed miR-223 caused NMDA-induced calcium influx inhibition (Harraz et al., 2012). | ||
| miR-222 | XLID individuals | Mutation found in pre-miRNA sequence (Chen et al., 2007). | |
| Small RNA libraries from 26 different organ systems and cell types of human and rodents (Landgraf et al., 2007) | X-chromosomal miRNAs expressed in the midbrain, the hippocampus, and the cortex (Mendoza et al., 2010). | ||
| miR-363 | XLID individuals | Mutation found in pre-miRNA sequence (Chen et al., 2007). | |
| FXR1P (Cheever et al., 2010) | |||
| Small RNA libraries from 26 different organ systems and cell types of human and rodents (Landgraf et al., 2007) | X-chromosomal miRNAs expressed in the midbrain (Mendoza et al., 2010). | ||
| HEK-293T cells | Downregulated the expression of FXR1P (Cheever et al., 2010). | ||
| miR-221 | Small RNA libraries from 26 different organ systems and cell types of human and rodents (Landgraf et al., 2007) | X-chromosomal miRNAs expressed in the hippocampus and the cortex (Mendoza et al., 2010). | |
| let-7f-2 | X-chromosomal miRNAs expressed in the midbrain, the hippocampus, and the cortex (Mendoza et al., 2010). | ||
| miR-19b-2 | X-chromosomal miRNAs expressed in the midbrain (Mendoza et al., 2010). | ||
| miR-92a-2, miR-374b | X-chromosomal miRNAs expressed in the midbrain and the hippocampus (Mendoza et al., 2010). | ||
| miR-98, miR-374a | X-chromosomal miRNAs expressed in the midbrain and the cortex (Mendoza et al., 2010). | ||
| miR-105-2 | X-chromosomal miRNAs expressed in the cortex (Mendoza et al., 2010). | ||
| miR-132 | E19 rat hippocampal neurons in culture | Overexpressed miR-132 led to stubby and mushroom dendritic spines with an increase in average protrusion width as well as the synaptic strength (Edbauer et al., 2010). | |
| miR-92b, miR-367 | HEK-293T cells | Downregulated the expression of FXR1P (Cheever et al., 2010). | |
| FXR1P (Cheever et al., 2010) | |||
| miR-9, miR-124 | fxr1 KO mice | Both pre-miR-9 and pre-miR-124 required FXR1P to efficiently process them into mature miRNAs in vitro (Xu et al., 2011). | |
| miR-19b, miR-302b*, miR-323-3p | HEK-293 cells | Potential repressors of the FMR1 gene (Yi et al., 2010). | |
| FMR1 (Yi et al., 2010) | |||
15-LOX, 15-lipoxygenase; AD, Alzheimer's disease; ANK2, ankyrin 2; CDKN2A, cyclin-dependent kinase inhibitor 2A; CTTNBP2, cortactin-binding protein 2; CFH, complement factor H; DS, Down syndrome; Dyrk1a, dual specificity tyrosine-phosphorylation-regulated kinase 1A; E19, embryonic day 19; EPHA4, Ephrin type A receptor 4; FMR1, fragile X mental retardation 1; fxr1, Farnesoid X receptor 1; FXR1P, fragile X related protein 1; GluR2, glutamate receptor, ionotropic, AMPA2 (alpha 2); IL-6, interleukin-6; iPSC, induced pluripotent stem cell; KO, knockout; MeCP2, methyl CpG binding protein 2; MHC-CnA, myosin heavy chain-calcineurin; Ncx1, sodium-calcium exchanger 1; NHA, normal human astrocytes; NMDA, N-methyl D-aspartate; NR2A, NMDA subunit 2A; NR2B, NMDA subunit 2B; P, postnatal; PICALM, phosphatidylinositol-binding clathrin assembly protein; SIRT1, sirtuin1; TGF-β, transforming growth factor-β; TLP7, toll-like receptor 7; TNF, tumor necrosis factor; UTR, untranslated region; WT, wildtype; XLID, X-linked intellectual disability;
*
denotes the passenger strand of a miRNA.