Noncoding RNA in Liver Regeneration—From Molecular Mechanisms to Clinical Implications

Sergeeva, Olga V.; Sviridov, Evgeny; Zatsepin, Timofei S.

doi:10.1055/s-0039-1693513

Cited by 11 publications

(7 citation statements)

References 214 publications

(207 reference statements)

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“…As a lot of lncRNA change expression during liver regeneration [ 42 ], we measured LL35 RNA levels after partial hepatectomy [ 26 ] and found its downregulation 2 h after surgery followed by an increase in the RNA level during the liver’s regeneration ( Figure 1 C). In addition, in our previous study we demonstrated ~70% decrease in the LL35 lncRNA level in mouse liver two weeks after the induction of fibrosis with carbon tetrachloride [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In Vivo

et al. 2022

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Glucose and lipid metabolism are crucial functional systems in eukaryotes. A large number of experimental studies both in animal models and humans have shown that long non-coding RNAs (lncRNAs) play an important role in glucose and lipid metabolism. Previously, human lncRNA DEANR1/linc00261 was described as a tumor suppressor that regulates a variety of biological processes such as cell proliferation, apoptosis, glucose metabolism and tumorigenesis. Here we report that murine lncRNA Falcor/LL35, a proposed functional analog of human DEANR1/linc00261, is predominantly expressed in murine normal hepatocytes and downregulated in HCC and after partial hepatectomy. The application of high-throughput approaches such as RNA-seq, LC-MS proteomics, lipidomics and metabolomics analysis allowed changes to be found in the transcriptome, proteome, lipidome and metabolome of hepatocytes after LL35 depletion. We revealed that LL35 is involved in the regulation of glycolysis and lipid biosynthesis in vitro and in vivo. Moreover, LL35 affects Notch and NF-κB signaling pathways in normal hepatocytes. All observed changes result in the decrease in the proliferation and migration of hepatocytes. We demonstrated similar phenotype changes between murine LL35 and human linc00261 depletion in vitro and in vivo that opens the opportunity to translate results for LL35 from a liver murine model to possible functions of human lncRNA linc00261.

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Section: Resultsmentioning

confidence: 99%

Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In Vivo

et al. 2022

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“…Liver regeneration may occur after partial hepatectomy, liver transplantation, viral infection, IRI or toxic injury. The regeneration process is complex and well-orchestrated (41,42), and it has been widely studied in order to understand the mechanisms that regulate hepatocyte proliferation and survival (43,44). In normal adult mouse liver, mature differentiated hepatocytes are not vegetative and are quiescent.…”

Section: Complement Cascades Are Essential In Liver Recovery and Regementioning

confidence: 99%

Emerging recognition of the complement system in hepatic ischemia/reperfusion injury, liver regeneration and recovery (Review)

Zhou

Lin

et al. 2021

Exp Ther Med

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Hepatic ischemia/reperfusion injury (IRI) is a result of the ischemic cascade and may occur in the settings of liver trauma, resection and transplantation. Components of the complement system have been indicated to be mediators of hepatic IRI and regulators of liver regeneration. As such, their potential to mediate both beneficial and harmful effects render them key targets for therapy. In the present study, the mechanisms of complement mediating hepatic IRI were discussed with a focus on the different functions of complement in hepatic injury and liver recovery, and an explanation for this apparent paradox is provided, i.e. that the complement products C3a and C5a have an important role in liver damage; however, C3a and C5a are also necessary for liver regeneration. Furthermore, situated at the end of the complement activation cascade, the membrane attack complex is crucial in hepatic IRI and inhibiting the complex with a site-targeted murine complement inhibitor, complement receptor 2-CD59, may improve liver regeneration after partial hepatectomy, even when hepatectomy is combined with ischemia and reperfusion. Contents 1. Introduction 2. Complement-mediated injury cascades in hepatic IRI 3. Complement cascades are essential in liver recovery and regeneration 4. Complement regulation between hepatic IRI and liver regeneration 5. Future perspective

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“…Parenchymal and mesenchymal cells, as well as several molecules including metabolites and cytokines, participate in this process (Lorente et al, 2020). The process of liver regeneration consists of three stages: the priming phase (0-6 h), proliferation phase (12-72 h), and termination phase (96-168 h) (Sergeeva et al, 2020). Due to high regeneration capacity, a healthy liver can achieve functional compensation within several weeks after 80% of the liver is resected (Yang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Amino acid metabolomics and machine learning for assessment of post-hepatectomy liver regeneration

Yan,

Chen,

Dai

et al. 2024

Front. Pharmacol.

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ObjectiveAmino acid (AA) metabolism plays a vital role in liver regeneration. However, its measuring utility for post-hepatectomy liver regeneration under different conditions remains unclear. We aimed to combine machine learning (ML) models with AA metabolomics to assess liver regeneration in health and non-alcoholic steatohepatitis (NASH).MethodsThe liver index (liver weight/body weight) was calculated following 70% hepatectomy in healthy and NASH mice. The serum levels of 39 amino acids were measured using ultra-high performance liquid chromatography–tandem mass spectrometry analysis. We used orthogonal partial least squares discriminant analysis to determine differential AAs and disturbed metabolic pathways during liver regeneration. The SHapley Additive exPlanations algorithm was performed to identify potential AA signatures, and five ML models including least absolute shrinkage and selection operator, random forest, K-nearest neighbor (KNN), support vector regression, and extreme gradient boosting were utilized to assess the liver index.ResultsEleven and twenty-two differential AAs were identified in the healthy and NASH groups, respectively. Among these metabolites, arginine and proline metabolism were commonly disturbed metabolic pathways related to liver regeneration in both groups. Five AA signatures were identified, including hydroxylysine, L-serine, 3-methylhistidine, L-tyrosine, and homocitrulline in healthy group, and L-arginine, 2-aminobutyric acid, sarcosine, beta-alanine, and L-cysteine in NASH group. The KNN model demonstrated the best evaluation performance with mean absolute error, root mean square error, and coefficient of determination values of 0.0037, 0.0047, 0.79 and 0.0028, 0.0034, 0.71 for the healthy and NASH groups, respectively.ConclusionThe KNN model based on five AA signatures performed best, which suggests that it may be a valuable tool for assessing post-hepatectomy liver regeneration in health and NASH.

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Noncoding RNA in Liver Regeneration—From Molecular Mechanisms to Clinical Implications

Cited by 11 publications

References 214 publications

Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In Vivo

Murine Falcor/LL35 lncRNA Contributes to Glucose and Lipid Metabolism In Vitro and In Vivo

Emerging recognition of the complement system in hepatic ischemia/reperfusion injury, liver regeneration and recovery (Review)

Amino acid metabolomics and machine learning for assessment of post-hepatectomy liver regeneration

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