Hepatitis B virus core protein promotes the expression of neuraminidase 1 to facilitate hepatocarcinogenesis

Kong, Fanyun; Li, Nan; Tu, Tao; Tao, Yukai; Bi, Yong‐Mei; Yuan, Dongchen; Zhang, Ning; Yang, Xiaoying; Kong, Delong; You, Hua; Zheng, Kuiyang; Tang, Renxian

doi:10.1038/s41374-020-0465-9

Cited by 16 publications

(14 citation statements)

References 36 publications

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“…A recent study indicated an association between NEU-1 and HCC ( 51 ). Notably increased mRNA and protein expression of NEU-1 was observed in HBV-related HCC tissues, and this increased expression was caused by the binding of the HBV core protein to NF-KB on the NEU-1 promoter, which led to downstream oncogenic signaling and epithelial-mesenchymal transition (EMT) in HCC cells, including Huh-7 and HepG2 cells ( 52 ). These findings indicated the involvement of NEU in the carcinogenesis of HCC.…”

Section: Discussionmentioning

confidence: 99%

Potential of antiviral drug oseltamivir for the treatment of liver cancer

et al. 2021

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Liver cancer is a leading cause of cancer-related mortality globally. Since hepatitis virus infections have been strongly associated with the incidence of liver cancer, studies concerning the effects of antiviral drugs on liver cancer have attracted great attention in recent years. The present study investigated the effects of two anti-hepatitis virus drugs, lamivudine and ribavirin, and one anti-influenza virus drug, oseltamivir, on liver cancer cells to assess alternative methods for treating liver cancer. MTT assays, wound healing assays, Τranswell assays, flow cytometry, immunoblotting, ELISA, immunofluorescence staining and a xenograft animal model were adopted to verify the effects of lamivudine, ribavirin and oseltamivir on liver cancer cells. Treatment with ribavirin and oseltamivir for 24 and 48 h significantly decreased the viability of both Huh-7 and HepG2 cells compared with that of THLE-3 cells in a dose-dependent manner. The subsequent investigations focused on oseltamivir, considering the more serious clinical adverse effects of ribavirin than those of oseltamivir. Significantly decreased migration and invasion were observed in both Huh-7 and HepG2 cells that were treated with oseltamivir for 24 and 48 h. In addition, oseltamivir significantly increased autophagy in Huh-7 cells, as revealed by the significantly higher ratios of LC3-II/LC3-I, increased expression of Beclin-1, and decreased expression of p62, whereas no significant increases in the expression of apoptosis-related proteins, including Apaf-1, cleaved caspase-3, and cleaved PARP-1, were detected. Notably, apoptosis and autophagy were significantly increased in HepG2 cells in the presence of oseltamivir, as revealed by the significant increases in the expression of Apaf-1, cleaved caspase-3, and cleaved PARP-1, the higher ratios of LC3-II/LC3-I, the increased expression of Beclin-1, and the decreased expression of p62. Additionally, significant inhibitory effects of oseltamivir on xenografted Huh-7 cells in athymic nude mice were observed. The present study, for the first time to the best of our knowledge, reported the differential effects of oseltamivir on inducing liver cancer cell death both in vitro and in vivo and may provide an alternative approach for treating liver cancer.

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Section: Discussionmentioning

confidence: 99%

Potential of antiviral drug oseltamivir for the treatment of liver cancer

et al. 2021

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“…Furthermore, we observed that the NEU1 expression was significantly related to the T stage, pathologic stages, and grades, and a trend toward increased NEU1 expression with advanced cancer stages or grades. Recently, it has been found that NEU1 promoted the proliferation and migration of HCC by activating intracellular signaling pathways (Kong et al, 2020), and siRNA-mediated silencing of NEU1 was related to the decrease of proliferation and migration of HCC cells (Hou et al, 2016). Also, it was observed that there was a discrepancy between male and female, and the underlying mechanism need further investigation.…”

Section: Discussionmentioning

confidence: 98%

Potential Role of NEU1 in Hepatocellular Carcinoma: A Study Based on Comprehensive Bioinformatical Analysis

Yang

et al. 2021

Front. Mol. Biosci.

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Background: Aberrant expression of NEU1 has been identified in many malignancies. Nevertheless, the clinical significance of NEU1 in hepatocellular carcinoma (HCC) has not been fully elucidated.Methods: In our study, multiple databases, including ONCOMINE, The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), Cancer Cell Line Encyclopedia (CCLE), Human Protein Atlas (HPA), Kaplan-Meier (KM) plotter, MethSurv, Gene Expression Profiling Interactive Analysis (GEPIA), and Metascape, etc., were utilized to investigate the expression, prognostic value, and function of NEU1 in HCC.Results: ONCOMINE, GEO, and TCGA analyses revealed that NEU1 was more highly expressed in HCC compared to normal tissues. Additionally, the mRNA and protein expression levels of NEU1 were increased in liver cancer cell lines and HCC tissues, respectively. Moreover, a trend toward increased NEU1 expression with advanced stage or grade was found. Furthermore, higher mRNA expression of NEU1 was found to be remarkably correlated with worse survival in HCC patients, and multivariate Cox analysis indicated that high mRNA expression of NEU1 was an independent prognostic factor for poor prognosis of HCC patients. Also, 21 methylated CpGs were found to be significantly related to HCC prognosis. Besides, functional enrichment analyses indicated that high NEU1 expression group had lower levels of B cells, CD8+ T cells, NK cells, and T helper cells, etc. than the low NEU1 expression group, and NEU1 may regulate a variety of tumor-related proteins and pathways, including lysosome, spliceosome, mTOR signaling pathway and so on.Conclusion: High expression level of NEU1 was positively correlated with unfavorable prognosis of HCC patients, which may be related to the regulation of cancer-associated pathways and the inhibition of immune function by NEU1. Thus, NEU1 could be used as a potential prognostic biomarker and target for HCC.

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“…According to the manufacturer's instruction, the cells were transfected with target plasmids with LipoMax DNA transfection reagents. Hepatoma cells stably transfected with Flag-HBc plasmids were selected with G418 [19].…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…Next, 100 μL cell suspension along with 100 μL Matrigel solution was injected into the mice at the shoulder. After fed for 14 days, the mice were killed, and the tumors were excised and analyzed as previously described [19].…”

Section: Animal Transplantationmentioning

confidence: 99%

Hepatitis B Virus Core Protein Mediates the Upregulation of C5α Receptor 1 via NF-κB Pathway to Facilitate the Growth and Migration of Hepatoma Cells

et al. 2021

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Purpose C5α receptor 1 (C5ΑR1) is associated with the development of various human cancers. However, whether it is involved in the development of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) is poorly understood. We explored the expression, biological role, and associated mechanisms of C5AR1 in HBV-related hepatoma cells. Materials and Methods The expression of C5ΑR1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor кB (NF-κB) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5ΑR1 in the activation of intracellular signal pathways, the upregulation of inflammatory cytokines, and the growth and migration of hepatoma cells mediated by HBc, were investigated. The effect of C5α in the development of HCC mediated by C5AR1 was also measured. Results C5ΑR1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5ΑR1 at the mRNA and protein levels. Besides, HBc could promote C5ΑR1 expression via the NF-κB pathway. Based on the C5ΑR1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Furthermore, C5ΑR1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5α could promote the malignant development of HBc-positive HCC via C5AR1. Conclusion We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5ΑR1 has a significant role in the functional abnormality of hepatoma cells mediated by HBc, and might be utilized as a potential therapeutic target for HBV-related HCC.

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Hepatitis B virus core protein promotes the expression of neuraminidase 1 to facilitate hepatocarcinogenesis

Cited by 16 publications

References 36 publications

Potential of antiviral drug oseltamivir for the treatment of liver cancer

Potential of antiviral drug oseltamivir for the treatment of liver cancer

Potential Role of NEU1 in Hepatocellular Carcinoma: A Study Based on Comprehensive Bioinformatical Analysis

Hepatitis B Virus Core Protein Mediates the Upregulation of C5α Receptor 1 via NF-κB Pathway to Facilitate the Growth and Migration of Hepatoma Cells

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