Human hepatic cell line 5: In-vitro model for hepatic immunobiology

Shrestha, Smeeta, Yeong, Ming Yue, Cheng, Xin Yi, Bhayana, Nidhi, Wang, Wei, Verma, Navin Kumar, Bao, Yongping and Wang, Yulan (2026) Human hepatic cell line 5: In-vitro model for hepatic immunobiology. Molecular Biology Reports, 53 (1). pp. 1-14. ISSN 0301-4851

Microsoft Word (OpenXML) (ss_2025DEC26_HHL5_Text and Figures final) - Accepted Version Available under License Unspecified licence. Download (1MB)

Abstract

Background: Hepatocellular carcinoma (HCC) remains a major global health burden, partly due to the lack of physiologically relevant in vitro models that accurately recapitulate early host-virus interactions and immune responses. Human Hepatocyte Line 5 (HHL-5) is an immortalized hepatocyte cell line that retains key liver-specific functions. This study aimed to characterize the phenotypic, genetic, and metabolic features of HHL-5 cells and evaluate their suitability as a non-cancerous hepatic model, in comparison with the HCC cell line HepG2. Methods and results: Morphological and phenotypic assessment of cells showed smaller cell and nuclear areas and slower proliferation with markedly longer doubling time of HHL-5 cells than HepG2 cells. Genomic analyses using whole-exome sequencing revealed enrichment of immune-related pathways in HHL-5 cells, including antigen processing and presentation, whereas HepG2 cells showed predominance of DNA replication pathways. Metabolomic profiling of cells by nuclear magnetic resonance spectroscopy showed hepatocyte-like oxidative profiles of HHL-5 cells, in contrast to the glycolytic phenotypes of HepG2 cells. Moreover, Western blotting for selected proteins showed reduced expression of oncogenic and stress-response markers, including c-Myc, pSTAT3, pNrf2, and select cytochrome P450 enzymes. Conclusion: Our findings support HHL-5 cells as a robust non-cancerous in vitro model for investigating liver diseases, viral infection, and early events in hepatocarcinogenesis. Clinical Trial Registration: Not applicable.

Item Type:	Article
Additional Information:	The data is deposited at NCBI – Bio Project ID PRJNA1069993. Author's Accepted Manuscript made available under UEA Rights Retention policy.
Uncontrolled Keywords:	genetic variants,hhl-5,hepg2,hepatocyte-like cells,metabolomics,virus,genetics,molecular biology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1311
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	10 Feb 2026 16:35
Last Modified:	13 Feb 2026 10:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101899
DOI:	10.1007/s11033-026-11502-w

Downloads

Actions (login required)

View Item