Increased Expression of RUNX1 in Liver Correlates with NASH Activity Score in Patients with Non-Alcoholic Steatohepatitis (NASH)

Kaur, Savneet; Rawal, Preety; Siddiqui, Hamda; Rohilla, Sumati; Sharma, Shvetank; Tripathi, Dinesh Mani; Baweja, Sukriti; Hassan, Mohsin; Vlaic, Sebastian; Guthke, Reinhard; Thomas, Maria; Dayoub, Rania; Bihari, C.; Sarin, Shiv Kumar; Weiss, Thomas S.

doi:10.3390/cells8101277

Cited by 32 publications

(40 citation statements)

References 36 publications

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“…Runx1 has been shown to regulate EMT via promoting the Wnt/β-catenin signaling pathway in colorectal cancer 41 . In addition, Runx1 played important role in liver fibrosis of non-alcoholic steatohepatitis patients 42 . Interestingly, Runx1 was found to regulate EMT marker genes in renal tubular epithelial cells, and deletion of Runx1 could attenuate renal fibrosis 43 .…”

Section: Discussionmentioning

confidence: 99%

LncRNA Hoxaas3 promotes lung fibroblast activation and fibrosis by targeting miR-450b-5p to regulate Runx1

et al. 2020

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Long noncoding RNAs (lncRNAs) participate in organ fibrosis and various pulmonary diseases, but its role in idiopathic pulmonary fibrosis (IPF) is not fully understood. In this study, we found lncRNA Hoxaas3 (Hoxaas3) was up-regulated in the mice model of BLM-induced PF and TGF-β1-induced fibrogenesis in lung fibroblasts (LF). Overexpression of Hoxaas3 promoted fibrogenesis, whereas Hoxaas3 inhibition attenuated lung fibrosis both in vitro and in vivo, through regulation of miR-450b-5p. Furthermore, miR-450b-5p inhibition stimulated fibrogenesis by regulating runt-related transcription factor 1 (Runx1), whereas up-regulation of miR-450b-5p alleviated fibrogenesis in LF. Mechanistically, our study showed that Hoxaas3 regulated lung fibroblast activation and fibrogenesis by acting as a competing endogenous RNA for miR-450b-5p: Hoxaas3 decreased the expression of miR-450b-5p to stimulate level and activity of Runx1 and induced fibrotic LF, whereas Runx1 inhibition alleviated the pro-fibrotic effect of Hoxaas3. In addition, Hoxaas3 was regulated by TGF-β1/Smad4 pathway as its transcriptional target. In conclusion, our study showed the role and mechanism of the TGF-β1/Smad4-Hoxaas3-miR-450b-5p-Runx1 axis for a better understanding of PF, demonstrated Hoxaas3 maybe a new diagnostic biomarker or potential therapeutic target for IPF.

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Section: Discussionmentioning

confidence: 99%

LncRNA Hoxaas3 promotes lung fibroblast activation and fibrosis by targeting miR-450b-5p to regulate Runx1

et al. 2020

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“…The expression of RUNX1 (also defined as acute myeloid leukemia 1 (AML1)) has correlated with the severity of NAFLD. The qRT-PCR and immunohistochemistry (IHC) analyses have shown that RUNX1 and its target gene, including CCL2 and PIK3CA , positively correlate to steatosis, fibrosis, and inflammation grade [ 90 ]. Knockdown of RUNX1 in the HUVEC cell line has affected mRNA expression of angiogenic and chemotactic factors and adhesion molecules such as VEGF, CCL2, PECAM1, and VCAM1.…”

Section: Potentiating Role Of Lncrnas In Nafldmentioning

confidence: 99%

A comprehensive review of long non-coding RNAs in the pathogenesis and development of non-alcoholic fatty liver disease

et al. 2021

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One of the most prevalent diseases worldwide without a fully-known mechanism is non-alcoholic fatty liver disease (NAFLD). Recently, long non-coding RNAs (lncRNAs) have emerged as significant regulatory molecules. These RNAs have been claimed by bioinformatic research that is involved in biologic processes, including cell cycle, transcription factor regulation, fatty acids metabolism, and-so-forth. There is a body of evidence that lncRNAs have a pivotal role in triglyceride, cholesterol, and lipoprotein metabolism. Moreover, lncRNAs by up- or down-regulation of the downstream molecules in fatty acid metabolism may determine the fatty acid deposition in the liver. Therefore, lncRNAs have attracted considerable interest in NAFLD pathology and research. In this review, we provide all of the lncRNAs and their possible mechanisms which have been introduced up to now. It is hoped that this study would provide deep insight into the role of lncRNAs in NAFLD to recognize the better molecular targets for therapy.

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“…Although not known in DILI specifically, increased expression of RUNX1 correlates with inflammation, fibrosis and NASH activity score in patients suffering from Non-Alcoholic Steatohepatitis (NASH) (46).…”

Section: Biological Interpretation Of Protein Targetsmentioning

confidence: 99%

Prediction and mechanistic analysis of Drug-Induced Liver Injury (DILI) based on chemical structure

Liu

Walter

Wright

et al. 2020

Preprint

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Background: Drug-induced liver injury (DILI) is a major safety concern characterized by a complex and diverse pathogenesis. In order to identify DILI early in drug development, a better understanding of the injury and models with better predictivity are urgently needed. One approach in this regard are in silico models which aim at predicting the risk of DILI based on the compound structure. However, these models do yet show sufficient predictive performance or interpretability to be useful for decision making by themselves, the former partially stemming from the underlying problem of labeling the in vivo DILI risk of compounds in a meaningful way for generating machine learning models.Results: As part of the Critical Assessment of Massive Data Analysis (CAMDA) “CMap Drug Safety Challenge” 2019 (http://papers.camda.info/), chemical structure-based models were generated using the binarized DILIrank annotations. Support Vector Machine (SVM) and Random Forest (RF) classifiers showed comparable performance to previously published models with a mean balanced accuracy over models generated using 5-fold cross-validation inside a 10-fold training scheme of 0.759±0.027 when predicting an external test set. In the models which used predicted protein targets as compound descriptors, we identified the most information-rich proteins which agreed with the mechanisms of action and toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs), one of the most important drug classes causing DILI, and the previously established stress response pathways mediated by mitochondria, p38 MAPK and TP53. In addition, we identified multiple proteins involved in xenobiotic metabolism which could be novel DILI-related off-targets, such as CLK1 and DDR2. Moreover, we derived potential structural alerts for DILI with high precision, including furan and hydrazine derivatives; however, all derived alerts were present in approved drugs and were over specific indicating the need to consider quantitative variables such as dose.Conclusion: Using chemical structure-based descriptors such as structural fingerprints and predicted protein targets, DILI prediction models were built with a predictive performance comparable to previous literature. In addition, we derived insights on proteins and pathways statistically (and potentially causally) linked to DILI from these models and inferred new structural alerts related to this adverse endpoint.

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Increased Expression of RUNX1 in Liver Correlates with NASH Activity Score in Patients with Non-Alcoholic Steatohepatitis (NASH)

Cited by 32 publications

References 36 publications

LncRNA Hoxaas3 promotes lung fibroblast activation and fibrosis by targeting miR-450b-5p to regulate Runx1

LncRNA Hoxaas3 promotes lung fibroblast activation and fibrosis by targeting miR-450b-5p to regulate Runx1

A comprehensive review of long non-coding RNAs in the pathogenesis and development of non-alcoholic fatty liver disease

Prediction and mechanistic analysis of Drug-Induced Liver Injury (DILI) based on chemical structure

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