Table 1.
MiRNAs implicated in type 2 diabetes and its oxidative stress-induced complications. Consequently, the restoration of miRNA expression to normal levels may represent an alternative therapeutic intervention to counteract oxidative damage.
| miRNA | Up/DownRegulation | Cell Type/Tissue | Target Gene | Effects | Reference |
|---|---|---|---|---|---|
| miR-200 family members | Up-regulation | HUVECs; in vivo mouse pancreatic β-cells |
SIRT1 PRDX2 |
Reduction of endothelial cell growth; elevated ROS production and apoptosis |
[62] |
| miR-200b/miR-200c | Down-regulation | HUVECs | ROCK2 | Elevated ROS production and apoptosis | [63,64] |
| miR-34 | Up-regulation | Type 2 diabetic db/db mice | SIRT1 | Vascular cells senescence | [65] |
| miR-106b | Up-regulation | Mouse pancreatic β-cell line NIT-1 cells |
SIRT1 | Increased oxidative stress | [66] |
| miR-204 | Up-regulation | HUVECs; C57/Bl6 mice |
SIRT1 CHOP ATF6 |
Endothelial dysfunction and vascular endoplasmic reticulum stress | [65] |
| miR-214 | Down-regulation | THP-1 cells | PTEN | Apoptosis and development of inflammatory responses | [67] |
| miR-205 | Down-regulation | Human renal tubular HK-2 cells | EGLN2 | Elevated ROS production and suppression of antioxidant enzymes |
[68] |
| miR-21 | Up-regulation | Human APCs | FoxO1 SOD2 |
Reduction of NO bioavailability and increased intracellular ROS levels | [69] |
| miR-375 | Down-regulation | MIN6 cells; INS-1E cells; miR-375−/−, Lep−/− (375/ob) mice; diabetic GK rats |
Aifm1 Pdk1 MTPN |
Attenuation of insulin release; reduction of β-cell mass and proliferation |
[70,71] |
| miR-182 miR-148 miR-2 6miR-24 |
Down-regulation | MIN6 cells; isolated primary islets |
Sox 6Bhlhe22 |
Down-regulation of insulin mRNA levels and insulin promoter activity | [72] |
| miR-30d | Down-regulation | Islets isolated from db/db mice | MAP4K4 MafA |
Inhibition of insulin production and release | [73,74] |
| miR-7 | Up-regulation | Transgenic mice; human islets from mildly T2D, obese non-diabetic, and control subjects |
mTOR | β-cell differentiation; impaired insulin release |
[75] |
| miR-9 | Up-regulation | MIN6 and dissociated islet cells | Onecut 2 | Inhibition of glucose-stimulated insulin exocytosis | [76] |
| miR-23a | |||||
| miR-149 | Down-regulation | Transgenic mice; skeletal muscle from HFD-fed obese mice | SIRT-1 PGC-1α |
Altered mitochondrial function and biogenesis | [77] |
| miR-141 | Down-regulation | Cardiac myocytes from diabetic mice | Slc25a3 | Alteration of mitochondrial function (ETC-complex V) |
[78] |
| miR-338 miR-210 miR-181c |
Down-regulation | Cardiac myocytes from diabetic rats | COX1 COXIV |
Alteration of mitochondrial function (ETC-complex IV) |
[79,80] |
| miR-210 | Down-regulation | H9c2 cardiomyocytes | ISCU COX10 |
Alteration of mitochondrial function (ETC-complex III) and up-regulation of glycolysis |
[81] |
Abbreviations: Aifm1, apoptosis inducing factor mitochondria associated 1; APCs, angiogenic progenitor cells; ATF6, activating transcription factor 6; Bhlhe22, Basic Helix-Loop-Helix Family Member E22; CHOP, C/EBP homologous protein; COX, cytochrome c oxidase; EGLN2, Egl nine homolog 2; ETC, electron transport chain; FoxO1, forkhead box protein O1; HUVECs, human umbilical vein endothelial cells; HO-1, heme oxygenase-1; IR, insulin resistance; ISCU, iron-sulfur cluster assembly enzyme; MafA, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A; MAP4K4, mitogen-activated protein kinase kinase kinase kinase 4; MTPN, myotrophin; mTOR, mammalian target of rapamycin; Pdk1, phosphoinositide 3-kinase-dependent-kinase; PGC-1α, peroxisome proliferator–activated receptor γ coactivator-1α; PRDX2, peroxiredoxin 2; PTEN, phosphatase and tensin homolog; ROCK2, RhoA/RhoA/Rho associated kinase 2; Slc25a3, solute carrier family 25 member 3; THP-1, human monocytic leukemia cell line; SIRT1, Sirtuin 1; SOD, superoxide dismutase; Sox6, SRY-Box transcription factor 6.