Comparison of Cardiac miRNA Transcriptomes Induced by Diabetes and Rapamycin Treatment and Identification of a Rapamycin-Associated Cardiac MicroRNA Signature

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 (, 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.