Knockdown of Decoy Receptor 3 Impairs Growth and Invasiveness of Hepatocellular Carcinoma Cell Line of HepG2

Zhou, Xiaona; Li, Guangming; Yang, Xu; Zhao, Tuanjie; Wu, Jixiang

doi:10.4103/0366-6999.192775

Cited by 14 publications

(9 citation statements)

References 24 publications

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“…In the present study, we examined the role of DcR3 in HCC development. Similar to the findings of both our study and that of Zhou et al 32 , DcR3 protein expression was found to be upregulated in HCC cells compared with adjacent non-tumour tissues, suggesting a role in the promotion of HCC development. Moreover, we detected an elevated level of DcR3 in the serum of HCC patients.…”

Section: Discussionsupporting

confidence: 92%

Role of TGFβ3-Smads-Sp1 axis in DcR3-mediated immune escape of hepatocellular carcinoma

Zhu

Liu

et al. 2019

Oncogenesis

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Hepatocellular carcinoma (HCC) is a leading cause of tumour-associated mortality worldwide, but no significant improvement in treating HCC has been reported with currently available systemic therapies. Immunotherapy represents a new frontier in tumour therapy. Therefore, the immunobiology of hepatocarcinoma has been under intensive investigation. Decoy receptor 3 (DcR3), a member of the tumour necrosis factor receptor (TNFR) superfamily, is an immune suppressor associated with tumourigenesis and cancer metastasis. However, little is known about the role of DcR3 in the immunobiology of hepatocarcinoma. In this study, we found that overexpression of DcR3 in HCC is mediated by the TGFβ3-Smad-Sp1 signalling pathway, which directly targets DcR3 promoter regions. Moreover, overexpression of DcR3 in HCC tissues is associated with tumour invasion and metastasis and significantly promotes the differentiation and secretion of Th2 and Treg cells while inhibiting the differentiation and secretion of Th1 cells. Conversely, knockdown of DcR3 expression in HCC significantly restored the immunity of CD4 + T cells. Inhibition of DcR3 expression may provide a novel immunotherapeutic approach to restoring immunity in HCC patients.

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Section: Discussionsupporting

confidence: 92%

Role of TGFβ3-Smads-Sp1 axis in DcR3-mediated immune escape of hepatocellular carcinoma

Zhu

Liu

et al. 2019

Oncogenesis

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“…In our previous study ( 27 ), HepG2 cells were successfully transfected with target lentivirus Lv-DcR3-EGFP-shRNA [the sequence with a stem-loop structure was CGCTGGTTTCTGCTTGGAGCA-CTCGAG-TGCTCCAAGCAGAAACCAGCG (Beijing TransGen Biotech, Co., Ltd., Beijing, China)] and blank lentivirus Lv-NC-EGFP-shRNA(Beijing TransGen Biotech, Co., Ltd.) using the Lipofectamine 2000 reagent (Invitrogen; Thermo Fisher Scientific, Inc.). The ratio of plasmid DNA (µg)/Lipofectamine 2000 reagent (µl) was 1:3.5, and DcR3 siRNA knockdown in HepG2 cells (KD) was achieved and DcR3 blank plasmid negative control HepG2 cells were utilized (negative control, NC).…”

Section: Methodsmentioning

confidence: 89%

“…Our previous study by the current study transfected human liver cancer HepG2 cells with lentivirus-based short hairpin RNA vector targeting DcR3 stably and indicated the that loss of DcR3 impaired the growth and invasive ability of HepG2 ( 27 ). The present study also used the HepG2 cell line, which was established in 1979 and mistakenly reported as a hepatocellular carcinoma cell line ( 28 ).…”

Section: Introductionmentioning

confidence: 84%

The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells

et al. 2018

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Dysfunctional Fas ligand (FasL) may inhibit the apoptosis of tumor cells. FasL contains two receptors, Fas and Decoy Receptor 3 (DcR3). DcR3 competitively binds to FasL over Fas, resulting in the inhibition of FasL-mediated apoptosis. Therefore, it was suggested that the downregulation of DcR3 expression enhances FasL-mediated apoptosis. In the current study, the expression of DcR3 was silenced in liver cancer HepG2 cells in order to study the effect of FasL on HepG2 cell activity and invasiveness. DcR3 siRNA knockdown HepG2 cells (KD), DcR3 blank plasmid control HepG2 cells and wild-type HepG2 cells (WT) were treated with FasL (10 ng/ml). Flow cytometry was used to detect changes in the cell cycle and apoptosis. MTS, clonogenic, wound healing and Transwell assays were performed to examine changes in cell activity, proliferation, migration and invasiveness. Reverse transcription polymerase chain reaction and western blot analysis were performed to measure the expression of DcR3, matrix metallopeptidase 9 (MMP9), vascular endothelial growth factor (VEGF)-C and VEGF-D. The results demonstrated that, compared with WT cells, the proportion of KD cells in the G2/M phase decreased following treatment with FasL. KD cells were more sensitive to FasL-induced apoptosis. Following treatment with FasL, the activity and proliferation, migration and invasion of KD cells were reduced, and the expression of MMP9, VEGF-C and VEGF-D decreased. Furthermore, it was demonstrated that DcR3 is involved in the proliferation and invasion of HepG2 cells, and this mechanism may be associated with the regulatory effect of the expression of MMP9, VEGF-C and VEGF-D; however, the exact mechanism of action remains unclear. FollowingDcR3 silencing, FasL-mediated apoptosis increased in HepG2 cells. Therefore, DcR3 combined with FasL may be a potential target for the treatment of liver cancer.

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“…35 Moreover, one study identified a receptor that acts as a decoy ligand, thereby protecting tumor cells from apoptosis. 36 Several studies have confirmed that ncRNAs can assist tumors in achieving TIE by regulating the abovementioned molecules and proteins, which could disrupt the balance between antideath and pro-death signals (Table 1). For example, miR-195, miR-24-2 and miR-365 can downregulate the expression of Bcl-2 and promote the apoptosis of tumor cells in breast cancer, 37 while miR-125b and miR-106a can upregulate the expression of Bcl-2 to inhibit the apoptosis of leukemia cells and breast cancer cells and promote their proliferation and infiltration.…”

Section: Tumor Death Pathways and Tiementioning

confidence: 99%

Noncoding RNAs: the shot callers in tumor immune escape

Liu

Wang

Qiu

et al. 2020

Sig Transduct Target Ther

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Immunotherapy, designed to exploit the functions of the host immune system against tumors, has shown considerable potential against several malignancies. However, the utility of immunotherapy is heavily limited due to the low response rate and various side effects in the clinical setting. Immune escape of tumor cells may be a critical reason for such low response rates. Noncoding RNAs (ncRNAs) have been identified as key regulatory factors in tumors and the immune system. Consequently, ncRNAs show promise as targets to improve the efficacy of immunotherapy in tumors. However, the relationship between ncRNAs and tumor immune escape (TIE) has not yet been comprehensively summarized. In this review, we provide a detailed account of the current knowledge on ncRNAs associated with TIE and their potential roles in tumor growth and survival mechanisms. This review bridges the gap between ncRNAs and TIE and broadens our understanding of their relationship, providing new insights and strategies to improve immunotherapy response rates by specifically targeting the ncRNAs involved in TIE.

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Knockdown of Decoy Receptor 3 Impairs Growth and Invasiveness of Hepatocellular Carcinoma Cell Line of HepG2

Cited by 14 publications

References 24 publications

Role of TGFβ3-Smads-Sp1 axis in DcR3-mediated immune escape of hepatocellular carcinoma

Role of TGFβ3-Smads-Sp1 axis in DcR3-mediated immune escape of hepatocellular carcinoma

The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells

Noncoding RNAs: the shot callers in tumor immune escape

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