Table 6.
miRNAs associated with cardiac fibrosis, their overall effect on fibrosis/TGF-β signaling, and the predicted target genes along the TGF-β signaling pathway.
| MicroRNA | Assoc. with fibrosis (r 2, p value) | Fibrotic effect | Predicted gene targets in the TGF-beta signaling pathway† |
|---|---|---|---|
| hsa-miR-140 | 0.6443, 0.034 | Anti [1] | PITX2, BMP2 |
| hsa-miR-144 | −0.83, 0.002 | Anti [2, 3] | ACVR2B, SMAD9, ROCK1, BMPR1B, CDKN2B, ID4 |
| hsa-miR-155 | 0.639, 0.036 | Pro/anti∗ [4, 5] | ACVR1C, BMPR2, SMAD5, SMAD2, PPP2CA, GDF6, SP1, RPS6KB1 |
| hsa-miR-21 | 0.633, 0.039 | Pro [6–8] | ACVR2A, BMPR2, SMAD7, TGFB2 |
| hsa-miR-26b | 0.687, 0.02 | Pro/anti∗ [9, 10] | ACVR1C, BMPR1B, BMPR2, CREBBP, EP300, IFNγ, INHBA, INHBB, SMAD1, SMAD2 |
| hsa-miR-34b | 0.742, 0.008 | Pro [11] | ACVR2A, ACVR1C, FST, SMAD5, SMAD7, SMURF1, RPS6KB1 |
∗Physiological conditionally based effects. †Emphasis indicates the predicted effect that miRNA inactivation of that gene would have on fibrosis. Italic emphasis refers to decreased fibrosis. Underlined emphasis refers to increased fibrosis. Bold emphasis refers to effect dependent on ligand milieu. ACVR1C: activin receptor type-1C; ACVR2A: activin receptor type-2A; ACVR2B: activin receptor type-2B; BMP2: bone morphological protein-2; BMPR2: bone morphological protein receptor type-2; CDKN2B: cyclin-dependent kinase inhibitor 2B; CREBBP: cAMP response element-binding protein; EP300: E1A-associated protein p300; FST: follistatin; GDF6: growth differentiation factor 6; ID4: inhibitor of DNA-binding protein 4; IFNγ: interferon-gamma; INHBA: inhibin beta A subunit; INHBB: inhibin beta B subunit; PITX2: paired-like homeodomain transcription factor 2; PPP2CA: protein phosphatase 2 catalytic subunit alpha; ROCK1: Rho-associated coiled-coil-containing protein; RPS6KB1: ribosomal protein S6 kinase B1; SMURF1: SMAD-specific E3 ubiquitin protein ligase 1; TGFB2: transforming growth factor beta 2.