Up-regulation of S100A4 expression by HBx protein promotes proliferation of hepatocellular carcinoma cells and its correlation with clinical survival

Zhu, Kai; Huang, Wenwen; Wang, Wenju; Liao, Lili; Li, Shuo; Yang, Shi Yu; Xu, Jingyi; Li, Lin; Meng, Mingyao; Xie, Youhua; He, Shan; Tang, Weiwei; Zhou, Haodong; Liang, Luxin; Gao, Hui; Zhao, Yiyi; Hou, Zhen; Jinquan, Tan; Li, Ruhong

doi:10.1016/j.gene.2020.144679

Cited by 14 publications

(12 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Anju et al studied the role of epithelial mesenchymal trans-differentiation (EMT) in the development of human immunodeficiency virus (HIV)-1-associated nephropathy, and observed enhanced expression of FSP1/S100A4 in EMT from parietal epithelial cells to periglomerular cells or from tubular cells to peritubular cells [55]. More recently, Zhu et al reported that the HBx gene of hepatitis B virus (HBV) promotes the occurrence and development of liver cancer by up-regulating the expression of S100A4; therefore, the authors believe that S100A4 is a potential therapeutic target for HBV-induced liver cancer [56].…”

Section: Plos Pathogensmentioning

confidence: 99%

S100A4+ macrophages facilitate zika virus invasion and persistence in the seminiferous tubules via interferon-gamma mediation

Yang

Liu

et al. 2020

PLoS Pathog

View full text Add to dashboard Cite

Testicular invasion and persistence are features of Zika virus (ZIKV), but their mechanisms are still unknown. Here, we showed that S100A4+ macrophages, a myeloid macrophage subpopulation with susceptibility to ZIKV infection, facilitated ZIKV invasion and persistence in the seminiferous tubules. In ZIKV-infected mice, S100A4+ macrophages were specifically recruited into the interstitial space of testes and differentiated into interferon-γ-expressing M1 macrophages. With interferon-γ mediation, S100A4+ macrophages down-regulated Claudin-1 expression and induced its redistribution from the cytosol to nucleus, thus increasing the permeability of the blood-testis barrier which facilitated S100A4+ macrophages invasion into the seminiferous tubules. Intraluminal S100A4+ macrophages were segregated from CD8+ T cells and consequently helped ZIKV evade cellular immunity. As a result, ZIKV continued to replicate in intraluminal S100A4+ macrophages even when the spermatogenic cells disappeared. Deficiencies in S100A4 or interferon-γ signaling both reduced ZIKV infection in the seminiferous tubules. These results demonstrated crucial roles of S100A4+ macrophages in ZIKV infection in testes.

show abstract

Section: Plos Pathogensmentioning

confidence: 99%

S100A4+ macrophages facilitate zika virus invasion and persistence in the seminiferous tubules via interferon-gamma mediation

Yang

Liu

et al. 2020

PLoS Pathog

View full text Add to dashboard Cite

show abstract

“…This may be due to the silenced HBx protein. Previous studies have shown that there is a certain relationship between HBx and the expression of IPS-1 and PD-L1 [ 37 , 38 , 39 ], but the specific mechanism needs further study.…”

Section: Resultsmentioning

confidence: 99%

“…This may be due HBx protein. Previous studies have shown that there is a certain relationship and the expression of IPS-1 and PD-L1 [37][38][39], but the specific mechanism study. As it is well known, IPS-1 and RIG-1 trigger the signaling pathway o feron, which is an important part of antiviral activity in innate immunit interacts with IPS-1 and RIG-1 to inhibit the activation of type 1 interferon activates the T-cell costimulatory receptor CD28 [43,44].…”

Section: Il-12 Expression and Reversal Of Immnuosuppression In Hepato...mentioning

confidence: 91%

Codelivery of HBx-siRNA and Plasmid Encoding IL-12 for Inhibition of Hepatitis B Virus and Reactivation of Antiviral Immunity

Ren

Han

et al. 2022

Pharmaceutics

View full text Add to dashboard Cite

Chronic hepatitis B is a critical cause of many serious liver diseases such as hepatocellular carcinoma (HCC). The main challenges in hepatitis B treatment include the rebound of hepatitis B virus (HBV)-related antigen levels after drug withdrawal and the immunosuppression caused by the virus. Herein, we demonstrate that the HBV-related antigen can be effectively inhibited and antiviral immunity can be successfully reactivated through codelivery of the small interfering RNA (siRNA) targeting HBV X protein (HBx) and the plasmid encoding interleukin 12 (pIL-12) to hepatocytes and immune cells. After being treated by the siRNA/pIL-12 codelivery system, HBx mRNA and hepatitis B surface antigen (HBsAg) are dramatically reduced in HepG2.215 cells. More importantly, the downregulated CD47 and programmed death ligand 1 (PD-L1) and the upregulated interferon-β promoter stimulator-1 (IPS-1), retinoic acid-inducible gene-1 (RIG-1), CD80, and human leukocyte antigen-1 (HLA-1) in treated HepG2.215 cells indicate that the immunosuppression is reversed by the codelivery system. Furthermore, the codelivery system results in inhibition of extracellular regulated protein kinases (ERK) and phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) pathways, as well as downregulation of B-cell lymphoma-2 (Bcl-2) and upregulation of p53, implying its potential in preventing the progression of HBV-induced HCC. In addition, J774A.1 macrophages treated by the codelivery system were successfully differentiated into the M1 phenotype and expressed enhanced cytokines with anti-hepatitis B effects such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α). Therefore, we believe that codelivery of siRNA and pIL-12 can effectively inhibit hepatitis B virus, reverse virus-induced immunosuppression, reactivate antiviral immunity, and hinder the progression of HBV-induced hepatocellular carcinoma. This investigation provides a promising approach for the synergistic treatment of HBV infection.

show abstract

“…Hepatitis B X protein (HBx) is encoded by HBV, and it has been demonstrated that HBx is closely linked to HBV-related HCC [20]. HBx plays a multifunctional role in common biochemical pathways by modulating the expression and activities of numerous genes, contributing to many pathological processes, including viral replication, gene transcription, signal transduction and protein degradation, which are ultimately linked to the occurrence and development of HCC [21,22].…”

Section: Discussionmentioning

confidence: 99%

A preoperative nomogram predicts prognosis of patients with hepatocellular carcinoma after liver transplantation: a multicenter retrospective study

et al. 2021

View full text Add to dashboard Cite

Background Although criteria for liver transplantation, such as the Milan criteria and Hangzhou experiences, have become popular, criteria to guide adjuvant therapy for patients with hepatocellular carcinoma after liver transplantation are lacking. Methods We collected data from all consecutive patients from 2012 to 2019 at three liver transplantation centers in China retrospectively. Univariate and multivariate analyses were used to analyze preoperative parameters, such as demographic and clinical data. Using data obtained in our center, calibration curves and the concordance Harrell’s C-indices were used to establish the final model. The validation cohort comprised the patients from the other centers. Results Data from 233 patients were used to construct the nomogram. The validation cohort comprised 36 patients. Independent predictors of overall survival (OS) were identified as HbeAg positive (P = 0.044), blood-type compatibility unmatched (P = 0.034), liver transplantation criteria (P = 0.003), and high MELD score (P = 0.037). For the validation cohort, to predict OS, the C-index of the nomogram was 0.874. Based on the model, patients could be assigned into low-risk (≥ 50%), intermediate-risk (30–50%), and high-risk (≤ 30%) groups to guide adjuvant therapy after surgery and to facilitate personalized management. Conclusions The OS in patients with hepatocellular carcinoma after liver transplantation could be accurately predicted using the developed nomogram.

show abstract

Up-regulation of S100A4 expression by HBx protein promotes proliferation of hepatocellular carcinoma cells and its correlation with clinical survival

Cited by 14 publications

References 26 publications

S100A4+ macrophages facilitate zika virus invasion and persistence in the seminiferous tubules via interferon-gamma mediation

S100A4+ macrophages facilitate zika virus invasion and persistence in the seminiferous tubules via interferon-gamma mediation

Codelivery of HBx-siRNA and Plasmid Encoding IL-12 for Inhibition of Hepatitis B Virus and Reactivation of Antiviral Immunity

A preoperative nomogram predicts prognosis of patients with hepatocellular carcinoma after liver transplantation: a multicenter retrospective study

Contact Info

Product

Resources

About