Transfection of apoptosis related gene Fas ligand in human hepatocellular carcinoma cells and its significance in apoptosis

Chen, Jun; Su, Xian-shi; Jiang, Yong-Fang; Gong, Guozhong; Zheng, Yu; Li, Guiyuan

doi:10.3748/wjg.v11.i17.2653

Cited by 5 publications

(4 citation statements)

References 19 publications

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“…FasL is a key protein that triggers the extrinsic apoptosis pathway, and its expression is regulated by many transcriptional factors such as Jun, NF‐κB, NFAT, EGR‐3, and SP1 in human tumors . Previous studies demonstrated that transfection of FasL into HepG2 cells induces apoptosis . The extrinsic and intrinsic apoptotic pathways are mediated by different caspases.…”

Section: Discussionmentioning

confidence: 99%

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NFATc1 is a tumor suppressor in hepatocellular carcinoma and induces tumor cell apoptosis by activating the FasL‐mediated extrinsic signaling pathway

Shu

Zou

et al. 2018

Cancer Medicine

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Nuclear factor of activated T cells (NFAT) is a family of transcription factors that have important functions in many tumors. However, the expression level and functional role of NFAT in hepatocellular carcinoma (HCC) remain unclear. In this study, we showed that NFATc1 expression was decreased in both HCC tissues and cell lines. Low expression of NFATc1 was correlated with larger tumor size, advanced tumor‐node‐metastasis (TNM) stage, high serum AFP level, and liver cirrhosis. Furthermore, patients with low NFATc1 expression exhibited poor prognosis. Ectopic expression of NFATc1 in HCC cells inhibited proliferation and colony formation, leading to G1 arrest and induction of apoptosis. In addition, we demonstrated that NFATc1 increased Fas ligand (FasL) expression by directly binding to its promoter and activated the extrinsic apoptotic pathway. NFATc1 and FasL expression patterns and their prognostic value for patients with HCC were also evaluated in TCGA Liver Hepatocellular Carcinoma database. Knock‐down of FasL expression by siRNA in HCC cell lines abolished NFATc1's antiproliferative and pro‐apoptotic effects. In conclusion, NFATc1 is frequently inactivated in HCC and functions as a tumor suppressor in liver carcinogenesis. Ectopic expression of NFATc1 in HCC cells induces apoptosis by activating the FasL‐mediated extrinsic signaling pathway.

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Section: Discussionmentioning

confidence: 99%

“…[44][45][46][47][48] Previous studies demonstrated that transfection of FasL into HepG2 cells induces apoptosis. 49 The extrinsic and intrinsic apoptotic pathways are mediated by different caspases. Caspase 8 is the initiator in the extrinsic apoptotic pathway, while caspase 9 is the initiator in the intrinsic apoptotic pathway.…”

Section: Discussionmentioning

confidence: 99%

NFATc1 is a tumor suppressor in hepatocellular carcinoma and induces tumor cell apoptosis by activating the FasL‐mediated extrinsic signaling pathway

Shu

Zou

et al. 2018

Cancer Medicine

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“…Consistent with this notion, FasL, an important trigger for Fasinduced cell death, is commonly seen elevated in liver tissue and serum in both patients with cirrhosis and HCC. However, higher levels of FasL were seen in patients with cirrhosis alone compared to those with HCC, and more abundant in peritumor tissue compared to tumor tissue within the diseased liver [114,116,117]. Other cytokines and chemokines which may play important roles in the progression phase of HCC, however, may be only minimally expressed or not present at all during the initial stages of the disease.…”

Section: Non-cellular Factors In the Hbv-associated Hcc Microenvironmentmentioning

confidence: 99%

The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma

Yang

Markowitz

Wang

2014

National Science Review

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In contrast to a majority of cancer types, the initiation of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue, with one of the most prevalent etiological factors being hepatitis B virus (HBV). Transformation of the liver in HBV-associated HCC often follows from or accompanies long-term symptoms of chronic hepatitis, inflammation and cirrhosis, and viral load is a strong predictor for both incidence and progression of HCC. Besides aiding in transformation, HBV plays a crucial role in modulating the accumulation and activation of both cellular components of the microenvironment, such as immune cells and fibroblasts, and non-cellular components of the microenvironment, such as cytokines and growth factors, markedly influencing disease progression and prognosis. This review will explore some of these components and mechanisms to demonstrate both underlying themes and the inherent complexity of these interacting systems in the initiation, progression, and metastasis of HBV-positive HCC.

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“…Additionally, Pinti et al , reported an increase in the production of Fas with age [67], while the production of sFasL is consistently reduced [67] and suggested a dissociation between the levels of sFas and sFasL. Further longitudinal studies are warranted in HBV-and HBV/HIV- infected patients to better understand the role sFas and sFasL are playing in HBV-mediated liver disease and whether there is any prognostic value in monitoring sFas and sFasL levels [46, 62, 68].…”

Section: Discussionmentioning

confidence: 99%

HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles

Shata

Abdel-hameed

Rouster

et al. 2019

PAI

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Background: Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to their shared routes of transmission, approximately 10% of HIV-infected patients worldwide are chronically coinfected with HBV. Additionally, liver disease has become a major cause of morbidity and mortality in HBV/HIV coinfected patients due to prolonged survival with the success of antiretroviral therapy. The relationship between immune exhaustion markers (PD-1/PD-L1) and apoptotic markers such as Fas/FasL, TGFβ1, TNF-α, and Th1/Th2 cytokines are not clearly delineated in HBV/HIV coinfection. Methods: Levels of soluble Fas/FasL, TGFβ1, TNF-α, and sPD-1/sPD-L1 as well as Th1 and Th2 cytokines were evaluated in the sera of HBV-monoinfected (n = 30) and HBV/HIV-coinfected (n = 15) patients and compared to levels in healthy controls (n = 20). Results: HBV-monoinfected patients had significantly lower levels of the anti-inflammatory cytokine IL-4 (P < 0.05) and higher levels of apoptotic markers sFas, sFasL, and TGFβ−1 (P < 0.001) compared to healthy controls. Coinfection with HIV was associated with higher levels of sFas, TNF-α, and sPD-L1 (P < 0.005), and higher levels of the pro-inflammatory cytokines IL-6, IL-8, and IL-12p70 (P < 0.05) compared to healthy controls. Patients with HBV infection had a unique biomarker clustering profile comprised of IFN-γ, IL12p70, IL-10, IL-6, and TNF-α that was distinct from the profile of the healthy controls, and the unique HIV/HBV profile comprised GM-CSF, IL-4, IL-2, IFN-γ, IL12p70, IL-7, IL-10, and IL-1β. In HBV monoinfection a significant correlation between sFasL and PD1(r = 0.46, P = < 0.05) and between sFas and PDL1 (r = 0.48, P = <0.01) was observed. Conclusion: HBV-infected and HBV/HIV-coinfected patients have unique apoptosis and inflammatory biomarker profiles that distinguish them from each other and healthy controls. The utilization of those unique biomarker profiles for monitoring disease progression or identifying individuals who may benefit from novel immunotherapies such as anti-PD-L1 or anti-PD-1 checkpoint inhibitors appears promising and warrants further investigation.

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Transfection of apoptosis related gene Fas ligand in human hepatocellular carcinoma cells and its significance in apoptosis

Abstract: Fas ligand is an apoptotic pathway of HCC cells.

Cited by 5 publications

References 19 publications

NFATc1 is a tumor suppressor in hepatocellular carcinoma and induces tumor cell apoptosis by activating the FasL‐mediated extrinsic signaling pathway

NFATc1 is a tumor suppressor in hepatocellular carcinoma and induces tumor cell apoptosis by activating the FasL‐mediated extrinsic signaling pathway

The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma

HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles

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