Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases
Abstract
:1. Introduction
2. Non-Coding RNAs Biogenesis and Function
2.1. Long Non-Coding RNAs
2.2. MicroRNAs
2.3. Circular RNAs
3. Non-Coding RNAs in Metabolic Diseases: State of Art
3.1. Long Non-Coding RNAs
3.1.1. Long Non-Coding RNAs and Obesity
3.1.2. Long Non-Coding RNAs and Type 2 Diabetes Mellitus
3.1.3. Long Non-Coding RNAs and NAFLD/NASH
3.2. Micro RNAs
3.2.1. MicroRNAs and Obesity
3.2.2. MicroRNAs and Type 2 Diabetes Mellitus
3.2.3. MicroRNAs and NAFLD/NASH
3.3. Circular RNAs
3.3.1. Circular RNAs and Obesity
3.3.2. Circular RNAs and Type 2 Diabetes Mellitus
3.3.3. Circular RNAs and NAFLD/NASH
4. Potential Clinical Application of Non-Coding RNAs
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Name | Functions | Targets |
---|---|---|
SRA | co-activator of PPARγ2 in adipogenesis [102]; promotes steatosis, ↓FFAs oxidation [102] | PPARγ2 [102]; FoxO1 [102] |
ASMER1, ASMER2 | adipogenesis, lipolysis, adiponectin secretion [103] | - |
ADNCR | adipocyte differentiation inhibition [104] | miRNA-204/SIRT1 [104] |
H19 | ↓expression of adipogenic factors [102]; inhibition of BMMSCs adipogenic differentiation [105]; promotes hepatic lipid accumulation [111]; promotes gluconeogenesis [102,112] | HDACs 4,5,6 [102]; miR-675/HDACs [105]; PTBP1/SREBP-1c [111]; FoxO1 [102], HNF4a [112] |
HOTAIR | promotes pre-adipocyte differentiation, ↑adipogenic genes expression (PPARγ and LPL) [101,106]; activates fibrogenesis and promotes TG accumulation [21] | Genes at HOXD locus [101]; MMP2, MMP9 [21] |
BlnC1 | ↑UCP1 expression, ↑ mitochondiral genes expression [3]; promotes adipose tissue browning [102] | Ebf2 [3,101,102] |
MALAT1 | ↑ROS and pro-inflammatory cytokines, promotes angiogenesis [112]; involved in the pathogenesis of diabetic gastroparesis [113]; promotes liver steatosis and fibrosis [21,102,114,115] | SAA3 [112]; α-SMA and SM-MHC [113]; CXCL5 [21,114,115] |
ANRIL | promotes atherosclerosis, ECs proliferation and adhesion [116]; causes cardiac dysfunction, myocardial apoptosis and fibrosis [117] | INK4B [116] |
MEG3 | promotes ECs functions, ↑microvascular permeability and inflammation upon silencing [116]; fibrosis progression upon downregulation, possibile interaction with HOTAIR [21] | PI3K/Akt [116] |
CASC2 | key role in renal tumorigenesis, possible involvement in renal failure [118] | - |
MIAT | ↑TNFa and VEGF, regulates ECs function [116] | miR-150-5p/VEGF [116] |
NONRATT021972 | involved in nociception and neuropathic pain ↑TNFa [119] | TNFa [119] |
lncARSR | ↑hepatic lipid accumulation [120] | PI3K/Akt /SREBP-1c [120] |
Lnc18q22.2 | associated with fibrosis and lobular inflammation [121,122] | - |
APTR | involved in collagen accumulation and HSCs activation [21] | - |
Name | Functions | Targets |
---|---|---|
miR-130 | ↓ adipogenesis [135] | PPARγ [135] |
miR-486 | ↑preadipocyte proliferation and myotube glucose intolerance [137] | preadipocyte [137] |
miR-146b and miR-15b | ↓glucose-stimulated insulin secretion [137] | - |
miR-375 | ↓GSIS process [138] | insulin gene transcription [138] |
miR-7 | ↓expression of genes involved in the process of fusion of insulin granules with plasma membrane and SNARE proteins [97] | genes involved in insulin granules fusion with plasma membrane and SNARE proteins [97] |
miR-184 | ↑ β-cell proliferation, ↑insulin secretion in response to glucose challenge and protects β-cells against apoptosis induced by chronic exposure to proinflammatory cytokines or FAs [139,140] | β-cells in pancreatic islets [139,140] |
miR-24 | implicated in de-differentiation and protection against apoptosis of β-cells [141] | β-cells in pancreatic islets [141] |
miR-204 | ↓insulin production [142]; ↑ improved glucose tolerance and insulin secretion [143] | TXNIP/miR-204/MafA/insulin pathway [142]; GLP1R [143] |
miR-122 | ↑Hepatocyte proliferation and maturation [144] ↓TG synthesis [145] | HNF6 [144] |
miR-29a | ↑Uptake of lipids from the circulation in hepatocytes [146] | Lpl [146] |
miR-21 | ↓TG, free cholesterol, and total cholesterol levels [147] ↑Lipid oxidation [148] | HMGCR and FABP7 [147,149]; PTEN [150]; PPARα [148] |
miR-33 | Cholesterol and FAs metabolism [151]; ↓Gluconeogenesis [152,153,154,155] | ABCA1 and ABCG1, CPT1A and AMPKα [151]; PCK1, G6PC [152,153,154,155] |
miR-34a | ↓FAs catabolism [156] | PPARα, SIRT1 [156] |
Name | Functions | Targets |
---|---|---|
circRNA_1897 | ↑Adipocytes differentiation and lipid metabolism [192] | miR-27a and miR-27b-3p [192] |
circRNA_26852 | Lipolysis and inhibition of adipocyte differentiation via a PPARγ-dependent mechanism [192] | miR-874 and miR-486 [192] |
circ_0046367 | Activation of genes involved in lipid metabolism such as Cpt2 and Acbd3 [193] | miR-34a/PPARα [193] |
circHIPK3 | ↑Lipid droplets accumulation following oleate treatment [194] | miR-192-5p/Foxo1 [194] |
circ_0001946(circCDR1) | ↑Adipogenic differentiation ↓Osteogenic differentiation of BMSCs [195]; ↓Insulin secretion [197] | miR-7-5p/Wnt5 [195]; miR-7/Snca, Cspa, Cplx1 [197] |
circRNA_0095570 (circH19) | ↓Lipids droplets formation and adipogenesis in ACDCs cells | Pparγ, Srebp1c and Cebp1- α |
circ_Arhgap5-2 | ↓Adipogenesis markers [196] | Pparγ, Cebpα, Fabp4 and AdipoQ [196] |
circRNA_0054633 | Biomarker of prediabetes in peripheral blood [198] | - |
circ_ANKRD36 | Potential role in inflammatory mechanisms occurring in T2D [199] | - |
circRNA_021412 | ↓long chain acyl-CoA synthetases and development of hepatic steatosis [200] | miR-1972/LPN1 [200] |
circRNA_0046366 | ↑Hepatocyte steatosis [193] | miR-34a/PPARα [193] |
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Formichi, C.; Nigi, L.; Grieco, G.E.; Maccora, C.; Fignani, D.; Brusco, N.; Licata, G.; Sebastiani, G.; Dotta, F. Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases. Int. J. Mol. Sci. 2021, 22, 7716. https://doi.org/10.3390/ijms22147716
Formichi C, Nigi L, Grieco GE, Maccora C, Fignani D, Brusco N, Licata G, Sebastiani G, Dotta F. Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases. International Journal of Molecular Sciences. 2021; 22(14):7716. https://doi.org/10.3390/ijms22147716
Chicago/Turabian StyleFormichi, Caterina, Laura Nigi, Giuseppina Emanuela Grieco, Carla Maccora, Daniela Fignani, Noemi Brusco, Giada Licata, Guido Sebastiani, and Francesco Dotta. 2021. "Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases" International Journal of Molecular Sciences 22, no. 14: 7716. https://doi.org/10.3390/ijms22147716