From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis

Mohr, Raphael; Özdirik, Burcin; Lambrecht, Joeri; Demir, Münevver; Eschrich, Johannes; Geisler, Lukas; Hellberg, Teresa; Loosen, Sven H.; Luedde, Tom; Tacke, Frank; Hammerich, Linda; Roderburg, Christoph

doi:10.3390/ijms22031492

Cited by 23 publications

(22 citation statements)

References 148 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The C-index of 0.702 of the nomogram indicated that the prediction and observation results matched perfectly [ 26 , 27 , 28 ]. The calibration plot revealed a straight line approaching the diagonal, indicating a strong correlation between the actual and estimated probabilities at 1.3 and 5 years ( Figure 8 A).…”

Section: Resultsmentioning

confidence: 99%

Significance of Identifying Key Genes Involved in HBV-Related Hepatocellular Carcinoma for Primary Care Surveillance of Patients with Cirrhosis

et al. 2022

Genes

View full text Add to dashboard Cite

Cirrhosis is frequently the final stage of disease preceding the development of hepatocellular carcinoma (HCC) and is one of the risk factors for HCC. Preventive surveillance for early HCC in patients with cirrhosis is advantageous for achieving early HCC prevention and diagnosis, thereby enhancing patient prognosis and reducing mortality. However, there is no highly sensitive diagnostic marker for the clinical surveillance of HCC in patients with cirrhosis, which significantly restricts its use in primary care for HCC. To increase the accuracy of illness diagnosis, the study of the effective and sensitive genetic biomarkers involved in HCC incidence is crucial. In this study, a set of 120 significantly differentially expressed genes (DEGs) was identified in the GSE121248 dataset. A protein–protein interaction (PPI) network was constructed among the DEGs, and Cytoscape was used to extract hub genes from the network. In TCGA database, the expression levels, correlation analysis, and predictive performance of hub genes were validated. In total, 15 hub genes showed increased expression, and their positive correlation ranged from 0.80 to 0.90, suggesting they may be involved in the same signaling pathway governing HBV-related HCC. The GSE10143, GSE25097, GSE54236, and GSE17548 datasets were used to investigate the expression pattern of these hub genes in the progression from cirrhosis to HCC. Using Cox regression analysis, a prediction model was then developed. The ROC curves, DCA, and calibration analysis demonstrated the superior disease prediction accuracy of this model. In addition, using proteomic analysis, we investigated whether these key hub genes interact with the HBV-encoded oncogene X protein (HBx), the oncogenic protein in HCC. We constructed stable HBx-expressing LO2-HBx and Huh-7-HBx cell lines. Co-immunoprecipitation coupled with mass spectrometry (Co-IP/MS) results demonstrated that CDK1, RRM2, ANLN, and HMMR interacted specifically with HBx in both cell models. Importantly, we investigated 15 potential key genes (CCNB1, CDK1, BUB1B, ECT2, RACGAP1, ANLN, PBK, TOP2A, ASPM, RRM2, NEK2, PRC1, SPP1, HMMR, and DTL) participating in the transformation process of HBV infection to HCC, of which 4 hub genes (CDK1, RRM2, ANLN, and HMMR) probably serve as potential oncogenic HBx downstream target molecules. All these findings of our study provided valuable research direction for the diagnostic gene detection of HBV-related HCC in primary care surveillance for HCC in patients with cirrhosis.

show abstract

Section: Resultsmentioning

confidence: 99%

Significance of Identifying Key Genes Involved in HBV-Related Hepatocellular Carcinoma for Primary Care Surveillance of Patients with Cirrhosis

et al. 2022

Genes

View full text Add to dashboard Cite

show abstract

“…However, such strategies do not: alleviate the damage to the immune system caused by anti-tumor treatment strategies; exert a protective effect upon lymphocytes; help to improve the function of the immune system; protect immune-related stem cells or blast cells. In addition, patients with advanced HCC are often accompanied by different degrees of fibrosis, cirrhosis, functional insufficiency of the liver or portal hypertension ( Behary et al, 2021 ; Mohr et al, 2021 ; Raza et al, 2021 ). Therefore, patients need continuous infusion of albumin and immune enhancement to prevent infection.…”

Section: Discussionmentioning

confidence: 99%

A Single Nucleotide Mixture Enhances the Antitumor Activity of Molecular-Targeted Drugs Against Hepatocellular Carcinoma

Mao

Jiang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

New strategies for molecular-targeted drug therapy for advanced hepatocellular carcinoma (HCC) ignore the contribution of the nutritional status of patients and nutritional support to improve physical status and immunity. We aimed to elucidate the role of a single nucleotide mixture (SNM) in the anti-tumor therapy of HCC, and to explore the importance of a SNM as adjuvant therapy for HCC. Compared with a lipid emulsion (commonly used nutritional supplement for HCC patients), the SNM could not induce metabolic abnormalities in HCC cells (Warburg effect), and did not affect expression of metabolic abnormality-related factors in HCC cells. The SNM could also attenuate the lymphocyte injury induced by antitumor drugs in vitro and in vivo, and promote the recruitment and survival of lymphocytes in HCC tissues. Using HCC models in SCID (server combined immune-deficiency) mice or BalB/c mice, the SNM had anti-tumor activity, and could significantly upregulate the antitumor activity of molecular-targeted drugs (tyrosine-kinase inhibitors [TKI] and immune-checkpoint inhibitors [ICI]) against HCC. We employed research models in vivo and in vitro to reveal the anti-tumor activity of the SNM on HCC. Our findings expand understanding of the SNM and contribute to HCC (especially nutritional support) therapy.

show abstract

“…Some of these miRNAs, which are involved in HBV transcription process, are also involved in the regulation of signaling pathways, disrupted in the cancer development. Among putative targets of miRNA-199a-3p are mTOR, c-Met, HIF-1α, CD44, ROCK1, and Axl, so this miRNA, being downregulated in miRNAs in Liver Cancer DOI: http://dx.doi.org/10.5772/intechopen.106171 liver cancer samples, may inhibit cell proliferation, migration, and invasion [69]. miRNA-184 may function as an anti-apoptotic factor in liver cancer, and INPPL1 was identified as one of its targets.…”

Section: Differential Expression Of Mirnas In Chronic Liver Diseasementioning

confidence: 99%

miRNAs in Liver Cancer

Petkevich¹,

Abramov²,

Pospelov³

2023

Liver Cancer - Genesis, Progression and Metastasis

View full text Add to dashboard Cite

miRNAs are small noncoding RNAs, which are involved in epigenetic regulation of gene expression. Hepatocellular carcinoma (HCC), although not being at the top of most widespread cancers, nevertheless, remains among cancers with the most lethal cases. The chapter is dedicated to the epigenetic aspect of HCC development, namely the role of miRNA in this process. Being small and noncoding RNAs, they have a huge and significant function in gene regulation. This chapter will briefly cover following questions: miRNA biogenesis and function, metabolic and signaling pathways disrupted in HCC with a significant miRNA involvement, and main miRNAs contributing to HCC development and their targets.

show abstract

From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis

Cited by 23 publications

References 148 publications

Significance of Identifying Key Genes Involved in HBV-Related Hepatocellular Carcinoma for Primary Care Surveillance of Patients with Cirrhosis

Significance of Identifying Key Genes Involved in HBV-Related Hepatocellular Carcinoma for Primary Care Surveillance of Patients with Cirrhosis

A Single Nucleotide Mixture Enhances the Antitumor Activity of Molecular-Targeted Drugs Against Hepatocellular Carcinoma

miRNAs in Liver Cancer

Contact Info

Product

Resources

About