Hepatitis B virus X protein promotes human hepatoma cell growth via upregulation of transcription factor AP2α and sphingosine kinase 1

Lu, Zhenzhen; Xiao, Zhiyong; Yang, Zhe; Li, Jiong; Feng, Guoxing; Chen, Fuquan; Li, Yinghui; Feng, Jinyan; Gao, Yuen; Ye, Lihong; Zhang, Xiaodong

doi:10.1038/aps.2015.38

Cited by 19 publications

(15 citation statements)

References 40 publications

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“…Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world [1] , and the second leading cause of cancer death, with 700 000 deaths annually [2][3][4] . Moreover, the dysregulation of various genes contributes to the development and progression of HCC, making it a sophisticated and intractable disease [5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

miR-511 promotes the proliferation of human hepatoma cells by targeting the 3′UTR of B cell translocation gene 1 (BTG1) mRNA

et al. 2017

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Aberrant expression of miR-511 is involved in the development of cancer, but the role of miR-511 in hepatocellular carcinoma (HCC) is not well documented. In this study, we explored the molecular mechanisms of miR-511 in hepatocarcinogenesis. Our results of bioinformatics analysis suggested that B cell translocation gene 1 (BTG1), a member of anti-proliferative gene family, was one of the putative targets of miR-511. The expression levels of miR-511 were significantly higher in 30 clinical HCC tissues than in corresponding peritumor tissues, and were negatively correlated with those of BTG1 in the HCC tissues (r=-0.6105, P<0.01). In human hepatoma cell lines HepG2 and H7402, overexpression of miR-511 dose-dependently inhibited the expression of BTG1, whereas knockdown of miR-511 dose-dependently increased the expression of BTG1. Luciferase reporter gene assays verified that miR-511 targeted the 3'UTR of BTG1 mRNA. In the hepatoma cells, overexpression of miR-511 significantly decreased BTG1-induced G phase arrest, which was rescued by overexpression of BTG1. Furthermore, overexpression of miR-511 promoted the proliferation of the hepatoma cells, which was rescued by overexpression of BTG1. Conversely, knockdown of miR-511 inhibited cell proliferation, which was reversed by knockdown of BTG1. In conclusion, miR-511 promotes the proliferation of human hepatoma cells in vitro by targeting the 3'UTR of BTG1 mRNA.

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Section: Introductionmentioning

confidence: 99%

miR-511 promotes the proliferation of human hepatoma cells by targeting the 3′UTR of B cell translocation gene 1 (BTG1) mRNA

et al. 2017

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“…Increased mRNA levels of hepatitis B virus (HBV) nonstructural protein, HBx, were positively correlated with an increase in SphK1 mRNA levels in clinical hepatocellular carcinoma patient tissues as well as HBx-transgenic mice [53]. A correlation was also discovered at the protein level utilizing these mice.…”

Section: Sphk1 In Virus Replicationmentioning

confidence: 89%

“…While many studies have been conducted using in vitro cell culture experimentation, several lines of investigation demonstrated the importance of S1P and its metabolizing enzymes during virus infections in humans or in vivo mouse models. For instance, SphK1 levels were shown to be increased in clinical hepatocellular carcinoma patient tissues as well as HBx-transgenic mice [53]. Modulation of SphK1/2 or S1P1 could confer protection to influenza virus-infected mice [60,66].…”

Section: Perspectivesmentioning

confidence: 99%

Emerging Connections of S1P-Metabolizing Enzymes with Host Defense and Immunity During Virus Infections

Wolf

Studstill

Hahm

2019

Viruses

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The sphingosine 1-phosphate (S1P) metabolic pathway is a dynamic regulator of multiple cellular and disease processes. Identification of the immune regulatory role of the sphingosine analog FTY720 led to the development of the first oral therapy for the treatment of an autoimmune disease, multiple sclerosis. Furthermore, inhibitors of sphingosine kinase (SphK), which mediate S1P synthesis, are being evaluated as a therapeutic option for the treatment of cancer. In conjunction with these captivating discoveries, S1P and S1P-metabolizing enzymes have been revealed to display vital functions during virus infections. For example, S1P lyase, which is known for metabolizing S1P, inhibits influenza virus replication by promoting antiviral type I interferon innate immune responses. In addition, both isoforms of sphingosine kinase have been shown to regulate the replication or pathogenicity of many viruses. Pro- or antiviral activities of S1P-metabolizing enzymes appear to be dependent on diverse virus–host interactions and viral pathogenesis. This review places an emphasis on summarizing the functions of S1P-metabolizing enzymes during virus infections and discusses the opportunities for designing pioneering antiviral drugs by targeting these host enzymes.

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“…Viruses manipulate cellular signalling. Examples of viral exploitation of SphK/S1P are influenza [ 217 ], measles [ 213 ], hepatitis B [ 218 ], dengue virus [ 219 ], the respiratory syncytial virus (RSV), hepatitis B virus (HBV), and hepatitis C viruses (HCV) [ 220 ].…”

Section: Targeting Sphk/s1p/s1pr In Viral Infection and Alleviatiomentioning

confidence: 99%

Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19

McGowan

Haddadi

Nassif

et al. 2020

IJMS

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The world is currently experiencing the worst health pandemic since the Spanish flu in 1918—the COVID-19 pandemic—caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the world’s third wake-up call this century. In 2003 and 2012, the world experienced two major coronavirus outbreaks, SARS-CoV-1 and Middle East Respiratory syndrome coronavirus (MERS-CoV), causing major respiratory tract infections. At present, there is neither a vaccine nor a cure for COVID-19. The severe COVID-19 symptoms of hyperinflammation, catastrophic damage to the vascular endothelium, thrombotic complications, septic shock, brain damage, acute disseminated encephalomyelitis (ADEM), and acute neurological and psychiatric complications are unprecedented. Many COVID-19 deaths result from the aftermath of hyperinflammatory complications, also referred to as the “cytokine storm syndrome”, endotheliitus and blood clotting, all with the potential to cause multiorgan dysfunction. The sphingolipid rheostat plays integral roles in viral replication, activation/modulation of the immune response, and importantly in maintaining vasculature integrity, with sphingosine 1 phosphate (S1P) and its cognate receptors (SIPRs: G-protein-coupled receptors) being key factors in vascular protection against endotheliitus. Hence, modulation of sphingosine kinase (SphK), S1P, and the S1P receptor pathway may provide significant beneficial effects towards counteracting the life-threatening, acute, and chronic complications associated with SARS-CoV-2 infection. This review provides a comprehensive overview of SARS-CoV-2 infection and disease, prospective vaccines, and current treatments. We then discuss the evidence supporting the targeting of SphK/S1P and S1P receptors in the repertoire of COVID-19 therapies to control viral replication and alleviate the known and emerging acute and chronic symptoms of COVID-19. Three clinical trials using FDA-approved sphingolipid-based drugs being repurposed and evaluated to help in alleviating COVID-19 symptoms are discussed.

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Hepatitis B virus X protein promotes human hepatoma cell growth via upregulation of transcription factor AP2α and sphingosine kinase 1

Cited by 19 publications

References 40 publications

miR-511 promotes the proliferation of human hepatoma cells by targeting the 3′UTR of B cell translocation gene 1 (BTG1) mRNA

miR-511 promotes the proliferation of human hepatoma cells by targeting the 3′UTR of B cell translocation gene 1 (BTG1) mRNA

Emerging Connections of S1P-Metabolizing Enzymes with Host Defense and Immunity During Virus Infections

Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19

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