PHD2 exerts anti-cancer and anti-inflammatory effects in colon cancer xenografts mice via attenuating NF-κB activity

Wang, Li; Niu, Zhendong; Wang, Xia; Li, Zhixi; Liu, Yanyang; Luo, Feng; Xi, Yan

doi:10.1016/j.lfs.2019.117167

Cited by 34 publications

(20 citation statements)

References 44 publications

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“…EMT has been identified as an early and important step in epithelial carcinoma. Activation of NF- κ B has been found to be a key promoter of EMT in liver cancer [ 31 ], colon cancer [ 32 ], gastric cancer [ 33 ], and various other cancers [ 34 ]. In the current study, functional assays illustrated that silencing RIPK4 in OC cell lines significantly restricted migratory and invasive properties.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of RIPK4 Expression Inhibits Epithelial-Mesenchymal Transition in Ovarian Cancer through IL-6

Lin

et al. 2021

Journal of Immunology Research

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RIPK4 has been implicated in multiple cancer types, but its role in ovarian cancer (OC) has not been clearly elucidated. Our data from Gene Expression Profiling Interactive Analysis, RT-PCR, and immunohistochemical analysis showed that RIPK4 was expressed at higher levels in OC tissues and cells than in normal ovarian tissues and cells. Increased RIPK4 expression in OC markedly correlated with a worse overall survival than lower RIPK4 expression levels (hazard rate (HR) 1.5 (1.45–1.87); P = 0.001 ). In functional experiments, RIPK4 downregulation significantly inhibited metastatic behaviours in OC cells. Subsequently, based on data from 593 OC patients in the TCGA database, gene set enrichment analysis revealed that RIPK4 was involved in epithelial-mesenchymal transition (EMT) in OC. At the molecular level, silencing RIPK4 significantly downregulated vimentin, N-cadherin, and Twist expression but induced an increase in the protein level of E-cadherin and inhibited the IL-6 and STAT3 levels. Moreover, IL-6 levels were significantly decreased in RIPK4-silenced OC cells ( P < 0.05 ). The addition of IL-6 to OC cells rescued the suppressive effect of RIPK4 knockdown on EMT. Thus, our data illustrate that downregulation of RIPK4 expression can restrain EMT in OC by inhibiting IL-6. This finding may provide a novel diagnostic and therapeutic target for improving the poor prognoses of OC patients.

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Section: Discussionmentioning

confidence: 99%

Downregulation of RIPK4 Expression Inhibits Epithelial-Mesenchymal Transition in Ovarian Cancer through IL-6

Lin

et al. 2021

Journal of Immunology Research

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“…Toll-like receptors (TLRs) have crucial roles in inflammation and cancer, and proteins downstream of the receptors, such as myeloid differentiation primary response 88 (MyD88) and NF-κB, enable cancer cells to escape from the immune system, which contributes to cancer progression (18). Notably, the inhibition of the NF-κB-mediated secretion of pro-inflammatory cytokines, including TNF-α, IL-6, IL-8, IL-1β and IL-4, has been revealed to decrease the volume of xenograft tumors and the accumulation of MDSCs (19). Therefore, blocking the TLR4/NF-κB signaling pathway and inhibiting MDSC recruitment may be an effective strategy for the treatment of numerous types of cancer.…”

Section: Introductionmentioning

confidence: 99%

Curcumin inhibits the growth of liver cancer by impairing myeloid‑derived suppressor cells in murine tumor tissues

et al. 2021

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Curcumin, one of the active ingredients of Curcuma longa (Jianghuang), has been reported to exert multiple bioactivities, including pro-apoptotic and anti-inflammatory activities. In recent years, curcumin has been extensively studied, and it has been revealed that curcumin inhibits the growth of numerous types of cancer. However, to the best of our knowledge, the inhibitory effects of curcumin on the activation or expansion of myeloid-derived suppressor cells (MDSCs) in liver cancer and the underlying mechanism have not yet been determined. Therefore, the present study aimed to investigate the inhibitory effect of curcumin on MDSC activity and the associated anti-neoplastic mechanism in a HepG2 ×enograft mouse model. The effect of curcumin on the viability of Huh-7, MHCC-97H and HepG2 cells in vitro was analyzed using a Cell Counting Kit-8 assay. The effects of curcumin on tumor growth, numbers of MDSCs, expression levels of proteins involved in the toll-like receptor 4 (TLR4)/NF-κB signaling pathway, levels of related inflammatory factors and angiogenesis were determined in HepG2 ×enograft model mice, which were given different doses of curcumin via intragastrical administration. The results of the present study revealed that curcumin inhibited the viability of Huh-7, MHCC-97H and HepG2 cells and the growth of HepG2 ×enograft tumors in mice. Flow cytometric analysis indicated that curcumin reduced the number of MDSCs in mouse xenograft tumors. In addition, the results demonstrated that curcumin inhibited the TLR4/NF-κB signaling pathway and the expression of inflammatory factors, including IL-6, IL-1β, prostaglandin E2 and cyclooxygenase-2, in mouse xenograft tumors. Furthermore, curcumin suppressed the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony stimulating factor (G-CSF), which are essential factors for MDSCs modulation, in tumor tissues. Additionally, curcumin was revealed to inhibit angiogenesis, which was demonstrated by the downregulation of the expression levels of vascular endothelial growth factor, CD31 and α-smooth muscle actin in western blotting, immunohistochemistry and immunofluorescence experiments. In conclusion, the findings of the present study identified a novel mechanism via which curcumin may suppress the growth of liver cancer by reducing the numbers of MDSCs and subsequently disrupting the process of angiogenesis. These conclusions were supported by the observed inactivation of the TLR4/NF-κB signaling pathway-mediated inflammatory response and the downregulation of GM-CSF and G-CSF secretion in xenograft tissues.

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“…Some cytokines, such as TNFα, IL-1 and EGF, can drive NF-κB activation ( 25 ). NF-κB activation inhibits apoptosis and promotes proliferation, invasion and inflammation in a variety of tumors ( 26 , 27 ). Therefore, we explored the relationship between FER and NF-κB in HCC.…”

Section: Discussionmentioning

confidence: 99%

FER Regulated by miR-206 Promotes Hepatocellular Carcinoma Progression via NF-κB Signaling

et al. 2021

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ObjectivesFeline sarcoma-related protein (FER) is known to play a critical regulatory role in several carcinomas. However, the exact biological function of FER in hepatocellular carcinoma (HCC) still needs to be investigated. The primary objective of this research was to investigate the unknown function and molecular mechanisms of FER in HCC.Materials and MethodsThe expression level of FER in HCC tissue samples and cells was examined by RT-qPCR, immunohistochemistry and western blot. Cellular and animal experiments were used to explore the effect of FER on the proliferative and metastatic capacities of HCC cells. The crosstalk between FER and NF-κB signaling was explored by western blot. The upstream factors that regulate FER were evaluated through dual-luciferase experiments and western blot assays.ResultsFER was overexpressed in HCC specimens and HCC cell lines. FER expression levels were positively associated with unfavorable clinicopathological characteristics. The higher the expression of FER was, the worse the overall survival of HCC patients was. The results of loss-of-function and gain-of-function experiments indicated that knockdown of FER decreased, while overexpression of FER increased, the proliferation, invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, we found that FER activated the NF-κB signaling pathway and stimulated epithelial-to-mesenchymal transition (EMT). We also found that FER was directly regulated by miR-206, and the downregulation of miR-206 was associated with proliferation and metastatic progression in HCC.ConclusionsThe present research was the first to reveal that a decrease in miR-206 levels results in an increase in FER expression in HCC, leading to enhanced cell growth and metastatic abilities via activation of the NF-κB signaling pathway.

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PHD2 exerts anti-cancer and anti-inflammatory effects in colon cancer xenografts mice via attenuating NF-κB activity

Cited by 34 publications

References 44 publications

Downregulation of RIPK4 Expression Inhibits Epithelial-Mesenchymal Transition in Ovarian Cancer through IL-6

Downregulation of RIPK4 Expression Inhibits Epithelial-Mesenchymal Transition in Ovarian Cancer through IL-6

Curcumin inhibits the growth of liver cancer by impairing myeloid‑derived suppressor cells in murine tumor tissues

FER Regulated by miR-206 Promotes Hepatocellular Carcinoma Progression via NF-κB Signaling

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