MiR-223 as a Regulator and Therapeutic Target in Liver Diseases

Gu, Jiarong; Xu, Hao; Chen, Yandong; Li, Na; Hou, Xin

doi:10.3389/fimmu.2022.860661

Cited by 23 publications

(17 citation statements)

References 89 publications

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“…MiRNAs are crucial organismal adjustment factors which come into play biological function and take part in a mass of pathophysiological processes by complementary nucleotide sequence-speci c binding to the 3′-UTR of the downstream mRNA to restrain translation process of target gene [29]. Several studies have provided evidence that various miRNAs adjust the process of hepatic brosis, including miR-98-5p and miR-34a [30,31], but no direct evidence demonstrated that miR-330-3p regulate the process of hepatic brosis.…”

Section: Discussionmentioning

confidence: 99%

Circ_0072088 mediates hepatic fibrosis renders epithelial to mesenchymal transition through miR-330-3p/CDK1 axis in AML12 hepatocytes

Liu

Xing

Jin

et al. 2022

Preprint

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Hepatic fibrosis was one of the causes to hepatocellular cancer (HCC), owing to limited therapeutic options. And hepatocytes can induce liver fibrogenesis via epithelial-mesenchymal transition (EMT). Multiple circRNAs exert critical role in the occurrence of liver fibrosis via working as microRNA (miRNA) sponges. Circ_0072088 is upregulated in hepatocellular cancer (HCC) and promote proliferation, migration of HCC cells. However, the potential research mechanism for circ_0072088 action against the fibrotic progression remain still unknown. The treatment of AML12 hepatocytes with TGF-β1 contributed to dramatically increased in the levels of circ_0072088. Additionally, in terms of mechanism, circ_0072088 was authenticated to function as miR-330-3p sponge, not only noticeable increase EMT, but also induced fibrosis in AML12 hepatocytes. MiR-330-3p could weaken the roles of circ_0072088 acceleration. Moreover, we proved that CDK1, a miR-330-3p target, was time-dependently augmented in the TGF-β1 treated AML12 hepatocytes, and its overexpression weakens the miR-330-3p regulatory effects.Our findings provided a unique role of the circ_0072088 mediates hepatic fibrosis renders epithelial-mesenchymal transition at least partially through miR-330-3p/CDK1 axis, thus suggesting its tremendous therapeutic potential in the treatment of liver diseases.

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Section: Discussionmentioning

confidence: 99%

Circ_0072088 mediates hepatic fibrosis renders epithelial to mesenchymal transition through miR-330-3p/CDK1 axis in AML12 hepatocytes

Liu

Xing

Jin

et al. 2022

Preprint

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Section: Methodsmentioning

confidence: 99%

“…promoter of miR-223 which further reduces TLR9/NF-kB-mediated inflammation by targeting IKKa expression(refer to Table 3) [74][75][76][77] .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…The organization is such that the activation of TLR9 up-regulates miR-223 by NF-kB binding on the promoter of miR-223 which further reduces TLR9/NF-kB-mediated inflammation by targeting IKKa expression (refer to ►Table 3). [74][75][76][77] In a study on bleomycin-treated mouse lung epithelial type II cells, Guo et al reported that decreased expression of miR-142-3p is associated with overexpression of COX2, increase in the apoptotic process, and inactivation of the PI3K/AKT/mTOR signaling pathway. 78 Acetaminophen is found to alter the expression of several miRNAs such as miR-298 and miR-370 which are found to regulate an oxidative stress-related gene.…”

Section: Molecular Basis Of Enhanced Reactive Oxygen Species Productionmentioning

confidence: 99%

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Genetic and Epigenetic Basis of Drug-Induced Liver Injury

et al. 2023

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Drug induced liver injury (DILI) is a rare but severe adverse drug reaction seen in pharmacotherapy and a major cause of post-marketing drug withdrawals. Advances in genome-wide studies indicate that genetic and epigenetic diversity can lead to inter-individual differences in drug response and toxicity. It is necessary to identify how the genetic variations, in the presence of environmental factors can contribute to development and progression of DILI. Studies on microRNA, histone modification and DNA methylation, SNPs related to DILI were retrieved from databases and were analyzed for the current research and updates develop this narrative review. We have compiled some of the major genetic, epigenetic, pharmacogenetic factors leading to DILI. Many validated genetic risk factors of DILI, such as variants of drug-metabolising enzymes, HLA alleles and some transporters were identified. In conclusion, these studies provide useful information in risk alleles identification and implementing personalised medicine.

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“…Intriguingly, genetic ablation of miR-223 exacerbates liver fibrosis in mice upon injury [ 15 , 16 ]. These results suggest miR-223 plays a protective role against fibrogenesis and could represent a new therapeutic target to combat with liver fibrosis [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-223 Suppresses Human Hepatic Stellate Cell Activation Partly via Regulating the Actin Cytoskeleton and Alleviates Fibrosis in Organoid Models of Liver Injury

Ariyachet

Chuaypen

Kaewsapsak

et al. 2022

IJMS

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MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate target mRNA expression, and altered expression of miRNAs is associated with liver pathological conditions. Recent studies in animal models have shown neutrophil/myeloid-specific microRNA-223 (miR-223) as a key regulator in the development of various liver diseases including fibrosis, where hepatic stellate cells (HSCs) are the key player in pathogenesis. However, the precise roles of miR-223 in human HSCs and its therapeutic potential to control fibrosis remain largely unexplored. Using primary human HSCs, we demonstrated that miR-223 suppressed the fibrogenic program and cellular proliferation while promoting features of quiescent HSCs including lipid re-accumulation and retinol storage. Furthermore, induction of miR-223 in HSCs decreased cellular motility and contraction. Mechanistically, miR-223 negatively regulated expression of smooth muscle α-actin (α-SMA) and thus reduced cytoskeletal activity, which is known to promote amplification of fibrogenic signals. Restoration of α-SMA in miR-223-overexpressing HSCs alleviated the antifibrotic effects of miR-223. Finally, to explore the therapeutic potential of miR-233 in liver fibrosis, we generated co-cultured organoids of HSCs with Huh7 hepatoma cells and challenged them with acetaminophen (APAP) or palmitic acid (PA) to induce hepatotoxicity. We showed that ectopic expression of miR-223 in HSCs attenuated fibrogenesis in the two human organoid models of liver injury, suggesting its potential application in antifibrotic therapy.

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MiR-223 as a Regulator and Therapeutic Target in Liver Diseases

Cited by 23 publications

References 89 publications

Circ_0072088 mediates hepatic fibrosis renders epithelial to mesenchymal transition through miR-330-3p/CDK1 axis in AML12 hepatocytes

Circ_0072088 mediates hepatic fibrosis renders epithelial to mesenchymal transition through miR-330-3p/CDK1 axis in AML12 hepatocytes

Genetic and Epigenetic Basis of Drug-Induced Liver Injury

MicroRNA-223 Suppresses Human Hepatic Stellate Cell Activation Partly via Regulating the Actin Cytoskeleton and Alleviates Fibrosis in Organoid Models of Liver Injury

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