The Multiple Roles of Hepatitis B Virus X Protein (HBx) Dysregulated MicroRNA in Hepatitis B Virus-Associated Hepatocellular Carcinoma (HBV-HCC) and Immune Pathways

Sartorius, Kurt; Swadling, Leo; An, Ping; Makarova, J. A.; Winkler, Cheryl A.; Chuturgoon, Anil A.; Kramvis, Anna

doi:10.3390/v12070746

Cited by 30 publications

(24 citation statements)

References 378 publications

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“…Furthermore, Singh et al identified a deregulated network of miRNAs-mRNAs in DCs that seems responsible for an impaired immune response during HBV pathogenesis [ 50 ]. Regarding adaptive immunity, several miRNAs such as miR-155, -17–92, -181a, and -21 have been linked to B and T cell activation and differentiation as well as Treg activity [ 51 ]. miR-155 expression positively correlates with T-cell activation in CHB patients and is a potential biomarker for immune activation and disease progression in HBV infection [ 52 ].…”

Section: Mirnas and The Immune System During Viral Hepatitismentioning

confidence: 99%

miRNAs as Potential Biomarkers for Viral Hepatitis B and C

Loureiro

Tout

Narguet

et al. 2020

Viruses

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Around 257 million people are living with hepatitis B virus (HBV) chronic infection and 71 million with hepatitis C virus (HCV) chronic infection. Both HBV and HCV infections can lead to liver complications such as cirrhosis and hepatocellular carcinoma (HCC). To take care of these chronically infected patients, one strategy is to diagnose the early stage of fibrosis in order to treat them as soon as possible to decrease the risk of HCC development. microRNAs (or miRNAs) are small non-coding RNAs which regulate many cellular processes in metazoans. Their expressions were frequently modulated by up- or down-regulation during fibrosis progression. In the serum of patients with HBV chronic infection (CHB), miR-122 and miR-185 expressions are increased, while miR-29, -143, -21 and miR-223 expressions are decreased during fibrosis progression. In the serum of patients with HCV chronic infection (CHC), miR-143 and miR-223 expressions are increased, while miR-122 expression is decreased during fibrosis progression. This review aims to summarize current knowledge of principal miRNAs modulation involved in fibrosis progression during chronic hepatitis B/C infections. Furthermore, we also discuss the potential use of miRNAs as non-invasive biomarkers to diagnose fibrosis with the intention of prioritizing patients with advanced fibrosis for treatment and surveillance.

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Section: Mirnas and The Immune System During Viral Hepatitismentioning

confidence: 99%

miRNAs as Potential Biomarkers for Viral Hepatitis B and C

Loureiro

Tout

Narguet

et al. 2020

Viruses

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“…In the HBV-HCC continuum, from asymptomatic HBV infection leading to HCC, an increasing number of miRNA are dysregulated due to the need to respond to viral infection, epigenetic changes ( 35 ), inflammation ( 128 ), fibrosis ( 129 ), cirrhosis ( 123 ) and finally, the onset of HCC. One of the most documented HBV tools to modulate both its own, as well as host genome expression is the HBx protein which has been shown to dysregulate multiple miRNA species in key HCC cancer and immune pathways ( 7 ).…”

Section: Hbv-hcc Pathogenesis: Role Of Mirnamentioning

confidence: 99%

“…HBx dysregulation of miR-155 can occur due to histone modifications like histone deacetylase inhibitors (HDAC-I) or the repression of polycomb proteins (EZH2) can contribute to upregulated miR-155 expression in HBV-HCC pathways ( 43 , 66 , 67 ). This well researched miRNA is cited as an epigenetic modulator in many cancers including those of the breast, lung and colon ( 195 – 197 ), as well as playing multiple different roles in both the innate and adaptive immune system response ( 7 ). In HBV-HCC pathogenesis, upregulated miR-155 typically represses PTEN modulation of AKT/MTOR signaling in the P13K/MAPK pathway that promotes epithelial to mesenchymal transition (EMT) ( 68 , 198 ).…”

Section: Hbx-dysregulated Mirna In Hbv-hcc Pathwaysmentioning

confidence: 99%

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The Epigenetic Modulation of Cancer and Immune Pathways in Hepatitis B Virus-Associated Hepatocellular Carcinoma: The Influence of HBx and miRNA Dysregulation

Sartorius

Winkler

et al. 2021

Front. Immunol.

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Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) pathogenesis is fueled by persistent HBV infection that stealthily maintains a delicate balance between viral replication and evasion of the host immune system. HBV is remarkably adept at using a combination of both its own, as well as host machinery to ensure its own replication and survival. A key tool in its arsenal, is the HBx protein which can manipulate the epigenetic landscape to decrease its own viral load and enhance persistence, as well as manage host genome epigenetic responses to the presence of viral infection. The HBx protein can initiate epigenetic modifications to dysregulate miRNA expression which, in turn, can regulate downstream epigenetic changes in HBV-HCC pathogenesis. We attempt to link the HBx and miRNA induced epigenetic modulations that influence both the HBV and host genome expression in HBV-HCC pathogenesis. In particular, the review investigates the interplay between CHB infection, the silencing role of miRNA, epigenetic change, immune system expression and HBV-HCC pathogenesis. The review demonstrates exactly how HBx-dysregulated miRNA in HBV-HCC pathogenesis influence and are influenced by epigenetic changes to modulate both viral and host genome expression. In particular, the review identifies a specific subset of HBx induced epigenetic miRNA pathways in HBV-HCC pathogenesis demonstrating the complex interplay between HBV infection, epigenetic change, disease and immune response. The wide-ranging influence of epigenetic change and miRNA modulation offers considerable potential as a therapeutic option in HBV-HCC.

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“…It has been found that heparin influences cell growth, differentiation, invasion, and migration and promotes the transcription of TXNIP in hepatoma cells by binding to the ChoRE-b site (70). Studies have also shown that chronic hepatitis B virus (HBV) infection is related to the occurrence and development of hepatocellular carcinoma (HCC) (77). It is well-known that HBV-related HCC is a global health problem (78).…”

Section: Cancers Of the Digestive Systemmentioning

confidence: 99%

Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers

et al. 2020

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Thioredoxin-interacting protein (TXNIP) is a thioredoxin-binding protein that can mediate oxidative stress, inhibit cell proliferation, and induce apoptosis by inhibiting the function of the thioredoxin system. TXNIP is important because of its wide range of functions in cardiovascular diseases, neurodegenerative diseases, cancer, diabetes, and other diseases. Increasing evidence has shown that TXNIP expression is low in tumors and that it may act as a tumor suppressor in various cancer types such as hepatocarcinoma, breast cancer, and lung cancer. TXNIP is known to inhibit the proliferation of breast cancer cells by affecting metabolic reprogramming and can affect the invasion and migration of breast cancer cells through the TXNIP-HIF1α-TWIST signaling axis. TXNIP can also prevent the occurrence of bladder cancer by inhibiting the activation of ERK, which inhibits apoptosis in bladder cancer cells. In this review, we find that TXNIP can be regulated by binding to transcription factors or other binding proteins and can also be downregulated by epigenetic changes or miRNA. In addition, we also summarize emerging insights on TXNIP expression and its functional role in different kinds of cancers, as well as clarify its participation in metabolic reprogramming and oxidative stress in cancer cells, wherein it acts as a putative tumor suppressor gene to inhibit the proliferation, invasion, and migration of different tumor cells as well as promote apoptosis in these cells. TXNIP may therefore be of basic and clinical significance for finding novel molecular targets that can facilitate the diagnosis and treatment of malignant tumors.

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The Multiple Roles of Hepatitis B Virus X Protein (HBx) Dysregulated MicroRNA in Hepatitis B Virus-Associated Hepatocellular Carcinoma (HBV-HCC) and Immune Pathways

Cited by 30 publications

References 378 publications

miRNAs as Potential Biomarkers for Viral Hepatitis B and C

miRNAs as Potential Biomarkers for Viral Hepatitis B and C

The Epigenetic Modulation of Cancer and Immune Pathways in Hepatitis B Virus-Associated Hepatocellular Carcinoma: The Influence of HBx and miRNA Dysregulation

Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers

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