MUC1 downregulation promotes TNF‐α‐induced necroptosis in human bronchial epithelial cells via regulation of the RIPK1/RIPK3 pathway

Zhang, Huojun; Jia-ni, JI; Liu, Qian; Xu, Shuyun

doi:10.1002/jcp.28148

Cited by 21 publications

(15 citation statements)

References 32 publications

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“…Generally, MUC1 is overexpressed at mucosal surfaces and absent in the skin epithelium and mesenchymal cells [26, 27]. Aberrantly glycosylated MUC1 is often overexpressed in most human epithelial cancers, but not reported in mesenchymal cell originated STS.…”

Section: Discussionmentioning

confidence: 99%

The construction and analysis of tumor-infiltrating immune cell and ceRNA networks in recurrent soft tissue sarcoma

Huang

Meng

Chen

et al. 2019

Aging

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Soft tissue sarcoma (STS) is one of the most challenging tumors for medical oncologists, with a high rate of recurrence after initial resection. In this study, a recurrent STS-specific competitive endogenous RNA (ceRNA) network including seven recurrence and overall survival (OS)-associated genes (LPP-AS2, MUC1, GAB2, hsa-let-7i-5p, hsa-let-7f-5p, hsa-miR-101-3p and hsa-miR-1226-3p) was established based on the gene expression profiling of 259 primary sarcomas and 3 local recurrence samples from the TCGA database. The algorithm “cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT)” was applied to estimate the fraction of immune cells in sarcomas. Based on 5 recurrence and OS-associated immune cells (NK cells activated, dendritic cells resting, mast cells resting, mast cells activated and macrophages M1), we constructed a recurrent STS-specific immune cells network. Both nomograms were identified to have good reliabilities (Area Under Curve (AUC) of 5-year survival is 0.724 and 0.773, respectively). Then the co-expression analysis was performed to identify the potential regulation network among recurrent STS-specific immune cells and ceRNAs. Hsa-miR-1226-3p and MUC1 were significantly correlated and dendritic cells resting was related to hsa-miR-1226-3p. Additionally, the expression of MUC1 and dendritic cell marker CD11c were also verified by immunohistochemistry (IHC) assay and multidimensional databases. In conclusion, this study illustrated the potential mechanism of hsa-miR-1226-3p regulating MUC1 and dendritic cells resting might play an important role in STS recurrence. These findings might provide potential prognostic biomarkers and therapeutic targets for recurrent STS.

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Section: Discussionmentioning

confidence: 99%

The construction and analysis of tumor-infiltrating immune cell and ceRNA networks in recurrent soft tissue sarcoma

Huang

Meng

Chen

et al. 2019

Aging

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“…It has been demonstrated that MUC1 plays an important, pathogen-specific, and potentially multifaceted role during respiratory infection [8,14,21,30,35]. MUC1 is an abundant constituent of the PCL where its extracellular domain contributes to airway surface hydration and its cytoplasmic domain has been shown to influence a variety of cellular signaling pathways that modulate the immune response [22,50], cell survival [51,52], and cancer progression [53]. Additionally, MUC1 expression and phosphorylation state depend on external inflammatory stimuli [23,24].…”

Section: Discussionmentioning

confidence: 99%

Membrane-Tethered Mucin 1 is Stimulated by Interferon in Multiple Cell Types and Antagonizes Influenza A Virus Infection in Human Airway Epithelium

Iverson

Song

et al. 2021

Preprint

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Influenza A virus (IAV) causes seasonal epidemics and periodic pandemics, resulting in significant morbidity and mortality in the human population. Tethered mucin 1 (MUC1) is highly expressed in airway epithelium, the primary site of IAV replication, and also by other cell types that influence IAV infection, including macrophages. MUC1 has the potential to influence infection dynamics through physical interactions and/or signaling activity, and recent work suggests MUC1 acts as a releasable decoy receptor and anti-inflammatory molecule during IAV infection. Still, the modulation of MUC1 and its impact during viral pathogenesis remains unclear. Thus, we sought to further investigate the interplay between MUC1 and IAV in an in vitro model of primary human airway epithelium (HAE). Our data indicate that a recombinant IAV hemagglutinin (H3) and H3N2 virus can bind endogenous HAE MUC1. We find that infection of HAE cultures with H1N1 or H3N2 IAV strains does not trigger enhanced MUC1 shedding, but instead stimulates an increase in cell-associated MUC1 protein. We observed a similar increase after stimulation with either type I or type III interferon (IFN); however, inhibition of IFN signaling during H1N1 infection only partially abrogated this increase, indicating multiple soluble factors contribute to MUC1 upregulation during the antiviral response. We expanded these findings and demonstrate that in addition to HAE, primary human monocyte-derived macrophages also upregulate MUC1 protein in response to both IFN treatment and conditioned media from IAV-infected HAE cultures. We then developed HAE genetically depleted for MUC1 to determine its impact on IAV pathogenesis, finding that MUC1 knock-out cultures exhibited enhanced viral growth compared to control cultures. Together, our data support a model whereby MUC1 antagonizes productive uptake of IAV in HAE. Infection then stimulates MUC1 expression on multiple cell types through IFN-dependent and -independent mechanisms that may further impact infection dynamics.

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“…The data were analyzed using Flowing version 2.5.3 software (Turku Bioscience) and Origin version 7 software (OriginLab). The results of a previous study have suggested that Annexin V-positive cells in the right quadrant are apoptotic, including the early and late apoptotic cells ( 20 ).…”

Section: Methodsmentioning

confidence: 97%

NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells

et al. 2021

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The results of a previous study demonstrated that heat stress (HS) triggered oxidative stress, which in turn induced the apoptosis of epithelial cells. These results uncovered a novel mechanism underlying the activation of NF-κB in primary human umbilical vein endothelial cells. The present study aimed to further investigate the role of NF-κB/IκBα signaling pathways in the inhibition of HS-induced reactive oxygen species (ROS) generation and cytotoxicity in endothelial cells. The results of the present study demonstrated that HS triggered a significant amount of NF-κB and IκBα nuclear translocation without IκBα degradation in a time-dependent manner. Mutant constructs of IκBα phosphorylation sites (Ser32, Ser36) were employed in rat pulmonary microvascular endothelial cells (PMVECs). Cell Counting Kit-8 assays demonstrated that both the small interfering (si)RNA-mediated knockdown of p65 and IκBα mutant constructs significantly decreased cell viability and aggravated ROS accumulation in HS-induced rat PMVECs compared with the control. Additionally, western blot analysis revealed that p65 siRNA attenuated the protein expression of IκBα. However, IκBα mutant constructs failed to attenuate NF-κB activation and nuclear translocation, indicating that IκBα-independent pathways contributed to NF-κB activity and nucleus translocation in a time-dependent manner following HS. Collectively, the results of the present study suggested that the NF-κB/IκBα pathway was essential for resistance to HS-induced ROS production and cytotoxicity in rat PMVECs, and that it could be a potential therapeutic target to reduce the mortality and morbidity of heat stroke.

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MUC1 downregulation promotes TNF‐α‐induced necroptosis in human bronchial epithelial cells via regulation of the RIPK1/RIPK3 pathway

Cited by 21 publications

References 32 publications

The construction and analysis of tumor-infiltrating immune cell and ceRNA networks in recurrent soft tissue sarcoma

The construction and analysis of tumor-infiltrating immune cell and ceRNA networks in recurrent soft tissue sarcoma

Membrane-Tethered Mucin 1 is Stimulated by Interferon in Multiple Cell Types and Antagonizes Influenza A Virus Infection in Human Airway Epithelium

NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells

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