Table 3.
miRNA | Evidence | Target Gene/Pathway | (Patho)Mechanism | References | |||
---|---|---|---|---|---|---|---|
In Vitro | In Vivo | In Situ | In Silico | ||||
21 ↑3 | ✓ | PPARα ↓ | Liver injury, inflammation and fibrosis | [75] | |||
21 ↑3 | ✓ | ✓ | ✓ | PTEN ↓ | Development of steatosis | [73] | |
21 ↑1 | ✓ | ✓ | TGFβ ↑ | Induced collagen production and extracellular matrix formation fibrogenesis via increase of Col1α1 and α-SMA expression | [72] | ||
122 ↑2 | ✓ | KLF6 ↑ | Activation of hepatic stellate cells and progression of liver fibrosis | [82] | |||
34a ↑2 | ✓ | ✓ | HNF4α ↓ | Inhibition of very low-density lipoprotein secretion and promotion of liver steatosis and hypolipidemia | [89] | ||
34a ↑1 | ✓ | ✓ | PPARα ↓ | Loss of regulation genes encoding fatty acid metabolizing enzymes and mitochondrial fatty acid oxidation activity | [87] | ||
34a ↑1 | ✓ | SIRT1 ↓ | Increase of hepatic cholesterol synthesis and activation of pro-apoptotic genes (p53, p66shc) | [88] | |||
29a and c ↓2 | ✓ | ✓ | SIRT1 ↓ | Increased levels of free cholesterol | [94,95] | ||
29 ↑2 | ✓ | ✓ | Col1α1 ↓ | Downregulation in activated hepatic stellate cells and therefore loss of interaction with Col1α1 → decreased collagen production |
[97] | ||
155 ↑1 | ✓ | ✓ | AKT/ FOXO3a ↑ |
Regulates proliferation of hepatic stellate cells promotes liver fibrosis; FOXO3a proteins maintain intracellular redox balance and survival | [99] | ||
155 ↑2 | ✓ | ✓ | LXRα ↓ | Decreased SREBP1 and FAS resulting in an increased intracellular lipid content | [100] | ||
155 ↑2 | ✓ | ✓ | HIF1α and vimentin ↑ | NASH-induced liver fibrosis | [101] |
Relation to oxidative stress: 1: yes, 2: no, 3: not mentioned. Abbreviations: AKT = Protein kinase B, Col1α1 = Collagen type I alpha 1, FAS = Fatty acid synthase, FOXO3 = Forkhead-Box-Protein O3, HIF1α = Hypoxia-inducible factor 1-alpha, HNF4α = Hepatocyte nuclear factor 4 alpha, KLF6 = Krueppel-like factor 6, LXRα = Liver X receptor alpha, PPARa = Peroxisome proliferator-activated receptor alpha, PTEN = Phosphatase and Tensin homolog, SIRT1 = Sirtuin 1, SREBP1 = sterol regulatory element-binding protein, ↓ = downregulation/reduction, ↑ = upregulation/increase.