scholarly journals Increased glucosylceramide production leads to decreased cell energy metabolism and lowered tumor marker expression in non-cancerous liver cells

2021 ◽  
Author(s):  
Marthe-Susanna Wegner ◽  
Nina Schömel ◽  
Ellen M. Olzomer ◽  
Sandra Trautmann ◽  
Catherine Olesch ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Molecular Mechanisms ◽  
Normal Liver ◽  
Liver Cells ◽  
New Therapeutic Approaches ◽  
Cell Energy ◽  
Murine Liver ◽  
Cancer Types ◽  
Cancer Phenotypes ◽  
Poor Outcomes

AbstractHepatocellular carcinoma (HCC) is one of the most difficult cancer types to treat. Liver cancer is often diagnosed at late stages and therapeutic treatment is frequently accompanied by development of multidrug resistance. This leads to poor outcomes for cancer patients. Understanding the fundamental molecular mechanisms leading to liver cancer development is crucial for developing new therapeutic approaches, which are more efficient in treating cancer. Mice with a liver specific UDP-glucose ceramide glucosyltransferase (UGCG) knockout (KO) show delayed diethylnitrosamine (DEN)-induced liver tumor growth. Accordingly, the rationale for our study was to determine whether UGCG overexpression is sufficient to drive cancer phenotypes in liver cells. We investigated the effect of UGCG overexpression (OE) on normal murine liver (NMuLi) cells. Increased UGCG expression results in decreased mitochondrial respiration and glycolysis, which is reversible by treatment with EtDO-P4, an UGCG inhibitor. Furthermore, tumor markers such as FGF21 and EPCAM are lowered following UGCG OE, which could be related to glucosylceramide (GlcCer) and lactosylceramide (LacCer) accumulation in glycosphingolipid-enriched microdomains (GEMs) and subsequently altered signaling protein phosphorylation. These cellular processes lead to decreased proliferation in NMuLi/UGCG OE cells. Our data show that increased UGCG expression itself does not induce pro-cancerous processes in normal liver cells, which indicates that increased GlcCer expression leads to different outcomes in different cancer types. Graphic abstract

A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy

2015 ◽  
Vol 1099 ◽  
pp. 18-23 ◽  
Author(s):  
Daping Sheng ◽  
Fangcheng Xu ◽  
Qiang Yu ◽  
Tingting Fang ◽  
Junjun Xia ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Ftir Spectroscopy ◽  
Cancer Cells ◽  
Normal Liver ◽  
Liver Cells ◽  
Liver Cancer Cells ◽  
Structural Differences

scholarly journals LncRNA NKILA Promotes Epithelial-Mesenchymal Transition of Liver Cancer Cells by Targeting miR-485-5p

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yuxu Wang ◽  
Chao Li ◽  
Yuyi Shi ◽  
Jing Kuai
Keyword(s):  
Liver Cancer ◽  
Normal Liver ◽  
Liver Cells ◽  
Luciferase Reporter Assay ◽  
Biological Behavior ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Mesenchymal Transition ◽  
The Relationship ◽  
Dual Luciferase Reporter Assay

Objective. Liver cancer (LC), one of the familiar malignancies, has a very high morbidity all over the world. The onset of the disease is hidden, and the patients usually do not express any special symptoms. Most of them will have been developed to the middle and later stage when they are diagnosed. This is one of the main reasons why the prognosis of LC is extremely pessimistic all the year round. Recently, researchers have focused mainly on molecular studies, among which LncRNA is a hot spot. This research aims to explore the biological behaviors of LncRNA NKILA and miR-485-5p in LC cells and verify the relationship between them, thereby providing a new theoretical basis for future prevention and treatment. Methods. Ninety-four early LC patients admitted to our hospital from January 2015 to January 2017 were regarded as the research objects. In addition, human LC cells SMMC-7721, HepG2, and normal liver cells HL-7702 were purchased. The LncRNA NKILA and miR-485-5p level in cancer and adjacent tissues, LC, and normal liver cells of patients was tested by PCR. Patients were followed up for 3 years. Then, LncRNA NKILA and miR-485-5p’s effects on prognosis and cell biological behavior were analyzed. At last, the relationship between LncRNA NKILA and miR-485-5p was assessed by a dual-luciferase reporter assay. Results. The LncRNA NKILA expression was high in LC tissues and cells ( P < 0.050 ), while miR-485-5p was low compared with the normal adjacent tissues ( P < 0.050 ). Prognostic follow-up manifested that high LncRNA NKILA or low miR-485-5p could predict the poor prognosis and high mortality risk of the patients ( P < 0.050 ). LC cells with downregulated LncRNA NKILA documented inhibited proliferation, invasion, and EMT, while the apoptosis level of the cells increased ( P < 0.050 ). The proliferation, invasion, and EMT were inhibited by miR-485-5p increase, while the apoptosis of the cells decreased after upregulating miR-485-5p ( P < 0.050 ). Online websites predicted that LncRNA NKILA had a binding site with miR-485-5p, and dual-luciferase reporter assay confirmed that LncRNA NKILA could directly target with miR-485-5p ( P < 0.050 ). The miR-485-5p in LC cells increased after LncRNA NKILA was silenced ( P < 0.050 ). The rescue experiment documented that LncRNA NKILA inhibition on LC cells was reversed by inhibiting miR-485-5p ( P < 0.050 ). Conclusion. The LncRNA NKILA with high expression advances LC cell proliferation, invasion, and EMT by targeting miR-485-5p.

Combination of ZnO Nanoparticle with Marine Sponge Derived Dipeptide for Enhanced Anticancer Efficacy in Liver Cancer Cells and their Toxicity Evaluation on Embryonic Zebrafish

2020 ◽  
Vol 16 ◽  
Author(s):  
Gayathri Karanam ◽  
Arumugam Madan Kumar ◽  
Chinmai Sriamulya Yerukalapudi ◽  
Nagabhishek Sirpu Natesh ◽  
Rajender Boddula ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Marine Sponge ◽  
Zno Nanoparticles ◽  
Normal Liver ◽  
Liver Cells ◽  
Zebrafish Embryos ◽  
Zno Nanoparticle ◽  
Anticancer Efficacy ◽  
Liver Cancer Cells

Background: Nanomaterials-based cancer therapy plays a significant role in increasing the therapeutic efficiency of anticancer drugs, reducing side effects and targeted delivery of the drug payloads. The present study was aimed to enhance the anticancer effect of a novel dipeptide isolated from marine sponge associated Bacillus pumilus AMK1 by formulating with Zinc oxide (ZnO) nanoparticles for the effective treatment against HepG2 liver cancer cells. Methods: The ZnO nanoparticles were synthesized by chemical method and size of the nanoparticle was characterized by Scanning electron microscope, X-Ray diffraction and Fourier-transform infrared spectroscopy. Further, The ZnO nanoparticles were conjugated with the isolated dipeptide and evaluated for anticancer activity. In addition, distinct morphological changes were observed by performing apoptotic staining methods such as propidium iodide staining and acridine orange/ ethidium bromide staining. Furthermore, embryotoxic and teratogenic effects of conjugated dipeptide on the development of zebrafish embryo were investigated in this study. Results: It was observed that conjugated dipeptide showed enhanced cytotoxicity against HepG2 liver cancer cells without any toxic effect on normal liver cells. ZnO with dipeptide showed a significant higher apoptosis of liver cancer cells with around 19% in early apoptosis and 53% in late apoptosis stage. The obtained results suggest that ZnO nanoparticle conjugated dipeptide initiated cytotoxicity through apoptotic death in HepG2 cells. The embryotoxic studies in zebrafish embryos revealed the LC50 197.0 µg/mL. These findings suggest that conjugated dipeptide affected the development of zebrafish embryos only at relatively higher concentrations. Conclusion: The experimental results demonstrate that Zno nanoparticle conjugated dipeptide has the potential to improve anticancer efficacy against liver cancer cells by inducing apoptosis in cancer cells without effecting normal liver cells.

scholarly journals High-Content Functional Screening of AEG-1 and AKR1C2 for the Promotion of Metastasis in Liver Cancer

2015 ◽  
Vol 21 (1) ◽  
pp. 101-107 ◽  
Author(s):  
Cong Li ◽  
Xia Wu ◽  
Wei Zhang ◽  
Jia Li ◽  
Huawei Liu ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Clinical Results ◽  
Functional Screening ◽  
Cancer Therapies ◽  
Kegg Pathway Database ◽  
Positive Regulators ◽  
Cancer Types ◽  
Insight Into

Liver cancer is one of the most lethal cancer types in humans, but our understanding of the molecular mechanisms underlying this process remains insufficient. Here, we conducted high-content screening of the potential genes involved in liver cancer metastasis, which we selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, based on the SAMcell method and RNA interference technology. We identified two powerful genes in the liver cancer metastasis process, AEG-1 and AKR1C2, both of which proved to be positive regulators in promoting metastasis in liver cancer. Further clinical results verified their roles in liver cancer. In summary, these findings could provide new insight into the liver cancer mechanism and potentially therapeutic novel targets for liver cancer therapies in the future.

scholarly journals Identification of Five Hub Genes as Key Prognostic Biomarkers in Liver Cancer via Integrated Bioinformatics Analysis

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 957
Author(s):  
Thong Ba Nguyen ◽  
Duy Ngoc Do ◽  
Tung Nguyen-Thanh ◽  
Vinay Bharadwaj Tatipamula ◽  
Ha Thi Nguyen
Keyword(s):  
Liver Cancer ◽  
Molecular Mechanisms ◽  
Normal Liver ◽  
Cyclin B1 ◽  
The Cancer Genome Atlas ◽  
Prognostic Biomarkers ◽  
Regulatory Subunit ◽  
Hub Genes ◽  
Topoisomerase Ii Alpha ◽  
Liver Tissues

Liver cancer is one of the most common cancers and the top leading cause of cancer death globally. However, the molecular mechanisms of liver tumorigenesis and progression remain unclear. In the current study, we investigated the hub genes and the potential molecular pathways through which these genes contribute to liver cancer onset and development. The weighted gene co-expression network analysis (WCGNA) was performed on the main data attained from the GEO (Gene Expression Omnibus) database. The Cancer Genome Atlas (TCGA) dataset was used to evaluate the association between prognosis and these hub genes. The expression of genes from the black module was found to be significantly related to liver cancer. Based on the results of protein–protein interaction, gene co-expression network, and survival analyses, DNA topoisomerase II alpha (TOP2A), ribonucleotide reductase regulatory subunit M2 (RRM2), never in mitosis-related kinase 2 (NEK2), cyclin-dependent kinase 1 (CDK1), and cyclin B1 (CCNB1) were identified as the hub genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the differentially expressed genes (DEGs) were enriched in the immune-associated pathways. These hub genes were further screened and validated using statistical and functional analyses. Additionally, the TOP2A, RRM2, NEK2, CDK1, and CCNB1 proteins were overexpressed in tumor liver tissues as compared to normal liver tissues according to the Human Protein Atlas database and previous studies. Our results suggest the potential use of TOP2A, RRM2, NEK2, CDK1, and CCNB1 as prognostic biomarkers in liver cancer.

scholarly journals HMGCS2 Mediates Ketone Production and Regulates the Proliferation and Metastasis of Hepatocellular Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1876 ◽  
Author(s):  
Yuan-Hsi Wang ◽  
Chao-Lien Liu ◽  
Wan-Chun Chiu ◽  
Yuh-Ching Twu ◽  
Yi-Jen Liao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Liver Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Survival Rates ◽  
Normal Liver ◽  
Apoptosis Pathway ◽  
Tissue Arrays

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor worldwide; however, the traditional therapeutic approaches and survival rates are still limited. To improve current therapies, it is necessary to investigate the molecular mechanisms underlying liver cancer and to identify potential therapeutic targets. The aims of this study were to verify the mechanisms and therapeutic potential of the ketogenesis rate-limiting enzyme 3-Hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) in HCC. Immunohistochemical staining of human liver disease tissue arrays showed that HMGCS2 is abundantly expressed in normal liver tissues but is downregulated in cirrhosis and HCC tissues. In HCC patients, lower HMGCS2 expression was correlated with higher pathological grades and clinical stages. In our investigation of the molecular mechanisms of HMGCS2 in HCC, we showed that knockdown of HMGCS2 decreased ketone production, which promoted cell proliferation, cell migration, and xenograft tumorigenesis by enhancing c-Myc/cyclinD1 and EMT signaling and by suppressing the caspase-dependent apoptosis pathway. Ketone body treatment reduced the proliferation- and migration-promoting effects of HMGCS2 knockdown in cells. In contrast, HMGCS2 overexpression increased the intracellular ketone level and inhibited cell proliferation, cell migration, and xenograft tumorigenesis. Finally, ketogenic diet administration significantly inhibited liver cancer cell growth in mice. Our studies highlight the potential therapeutic strategy of targeting HMGCS2-mediated ketogenesis in liver cancer.

scholarly journals Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1715
Author(s):  
Macus Hao-Ran Bao ◽  
Carmen Chak-Lui Wong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Liver Cancer ◽  
Effective Treatment ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Metabolic Reprogramming ◽  
Combination Therapies ◽  
Low Oxygen ◽  
Treatment Regimens

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

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