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. 2019 Oct 23;20(21):5266. doi: 10.3390/ijms20215266

Table 3.

Deregulated miRNAs and relation to OS in NAFLD/NASH.

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.