The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC

Rusu, Ioana; Pîrlog, Radu; Chiroi, Paul; Nuțu, Andreea; Puia, Vlad Radu; Fetti, Alin; Rusu, Daniel Radu; Berindan‐Neagoe, Ioana; Hajjar, Nadim Al

doi:10.3390/ijms232012370

Cited by 13 publications

(4 citation statements)

References 250 publications

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“…ceRNAs play a major role in the control of post-transcriptional gene expression in physiological and pathological contexts [46].In addition, miRNAs have been revealed to have an important role in liver disorders [12,47]. A regulatory network may also be involved in NASH [48,49]. A network of miRNA-mRNA interactions linked with UA-NASH was developed in this research.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Insight Based on Network Analysis Reveals the Effect of Ursolic Acid on Non-Alcoholic Steatohepatitis

Xue

Rao

et al. 2022

Preprint

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Background Non-alcoholic steatohepatitis (NASH) has attracted international attention. However, pharmaceutical treatments are not included in the current guidelines. Ursolic acid (UA) has the potential to treat metabolic disorders. Hence, this study aimed to investigate the impact of UA on NASH. Methods RNA sequencing from our own model mice was performed to detect differentially expressed genes (DEGs) in 12 mouse samples from 4 groups. DEGs were subjected to Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was applied to find modules associated with NASH's pathological characteristics and identified the hub genes in the relevant modules. Hub genes were further identified and the ceRNA network was constructed. In vitro and in vivo experiments were applied to identify the expected mRNAs. Results By comparing NASH mice to Wild type (WT) mice, we performed GO and KEGG enrichment analysis to identify pathways associated with NASH inflammatory metabolic disorders, and by doing the same for NASH mice treated with UA, we identified pathways via which UA may alter. Based on WGCNA, the modules associated with the pathological changes of NASH, as well as the hub genes in each module were identified. A ceRNA network was successfully constructed. RT-PCR results showed that Akr1a1 and Chchd2 were protective factors against NASH, and Ndufb9 was a risk factor. The level of ROS detected by flow cytometry indicated that UA could alleviate oxidative stress. Conclusion Akr1a1, Chchd2, and Ndufb9 were essential for the therapeutic effects of UA on NASH and the ceRNA network might act as prospective therapeutic and diagnostic biomarker targets.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Insight Based on Network Analysis Reveals the Effect of Ursolic Acid on Non-Alcoholic Steatohepatitis

Xue

Rao

et al. 2022

Preprint

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“…Given the worldwide obesity pandemic, a growing amount of evidence suggests that obesity and the accompanying development of non-alcoholic fatty liver disease (NAFLD) and its aggressive form non-alcoholic steatohepatitis (NASH) are becoming the leading contributing factors to the rising incidence of HCC ( 11 – 13 ). Notably, efforts are underway to rename NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD), which emphasizes the role of the metabolic syndrome, obesity and Type 2 diabetes mellitus (T2DM) in contributing to the burden of liver disease ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets

et al. 2023

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Obesity is a global epidemic and overwhelming evidence indicates that it is a risk factor for numerous cancers, including hepatocellular carcinoma (HCC), the third leading cause of cancer-related deaths worldwide. Obesity-associated hepatic tumorigenesis develops from nonalcoholic fatty liver disease (NAFLD), progressing to nonalcoholic steatohepatitis (NASH), cirrhosis and ultimately to HCC. The rising incidence of obesity is resulting in an increased prevalence of NAFLD and NASH, and subsequently HCC. Obesity represents an increasingly important underlying etiology of HCC, in particular as the other leading causes of HCC such as hepatitis infection, are declining due to effective treatments and vaccines. In this review, we provide a comprehensive overview of the molecular mechanisms and cellular signaling pathways involved in the pathogenesis of obesity-associated HCC. We summarize the preclinical experimental animal models available to study the features of NAFLD/NASH/HCC, and the non-invasive methods to diagnose NAFLD, NASH and early-stage HCC. Finally, since HCC is an aggressive tumor with a 5-year survival of less than 20%, we will also discuss novel therapeutic targets for obesity-associated HCC and ongoing clinical trials.

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“…Therefore, NAFLD‐related HCC cases are often diagnosed late and treatment options are limited. This highlights the need for a clearer understanding of the mechanisms involved in the transition from steatosis to liver cancer, which may help in the discovery of new biomarkers and the development of better screening methods (Rusu et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Coptidis rhizoma and evodiae fructus against lipid droplet deposition in nonalcoholic fatty liver disease‐related liver cancer by AKT

Hao

Deng

et al. 2023

Chem Biol Drug Des

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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. NAFLD has become one of the major factors contributing to hepatocellular carcinoma (HCC) development. However, there are no clear targets and therapeutic drugs for NAFLD‐related liver cancer. This study explored the active compounds, target and mechanism of coptidis rhizoma and evodiae fructus in the treatment of NAFLD‐related liver cancer based on the network pharmacology and experimental verification. There were 455 intersection targets of NAFLD‐related liver cancer, and 65 drug‐disease common targets. AKT1 has the highest degree, indicating that it may be a key target of coptidis rhizoma and evodiae fructus in the treatment of NAFLD‐related liver cancer. The expression level of AKT1 was high in high‐risk group, and the overall survival rate was lower than that in low‐risk group. After oleic acid induction, p‐AKT expression and lipid droplet deposition were promoted in HepG2 cells. Quercetin and resveratrol reduced lipid droplet deposition in vivo. Moreover, quercetin inhibited p‐AKT expression, resveratrol both reduced the expression of p‐AKT and AKT. The overall findings suggested that quercetin inhibited AKT in the treatment of NAFLD‐related liver cancer.

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The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC

Cited by 13 publications

References 250 publications

Transcriptomic Insight Based on Network Analysis Reveals the Effect of Ursolic Acid on Non-Alcoholic Steatohepatitis

Transcriptomic Insight Based on Network Analysis Reveals the Effect of Ursolic Acid on Non-Alcoholic Steatohepatitis

Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets

Coptidis rhizoma and evodiae fructus against lipid droplet deposition in nonalcoholic fatty liver disease‐related liver cancer by AKT

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