NF-κB regulates the expression of STING via alternative promoter usage

Chen, Lin-Yuan; Pang, Xiao‐Yu; Chen, Can; Xu, Hua‐Guo

doi:10.1016/j.lfs.2022.121336

Cited by 5 publications

(3 citation statements)

References 50 publications

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“…6L). In the Rare WGD context, our results are concordant with the hypothesis that CIN-associated cytosolic DNA activates NF-κB, which promotes transcription of STING 35 , and suppresses E2F targets 36,37 , ultimately leading to G1 arrest or delay.…”

Section: We Investigated How Chromosomal Instability Phenotypes Encod...supporting

confidence: 87%

Ongoing genome doubling promotes evolvability and immune dysregulation in ovarian cancer

McPherson,

Vázquez-García,

Myers

et al. 2024

Preprint

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Whole-genome doubling (WGD) is a critical driver of tumor development and is linked to drug resistance and metastasis in solid malignancies. Here, we demonstrate that WGD is an ongoing mutational process in tumor evolution. Using single-cell whole-genome sequencing, we measured and modeled how WGD events are distributed across cellular populations within tumors and associated WGD dynamics with properties of genome diversification and phenotypic consequences of innate immunity. We studied WGD evolution in 65 high-grade serous ovarian cancer (HGSOC) tissue samples from 40 patients, yielding 29,481 tumor cell genomes. We found near-ubiquitous evidence of WGD as an ongoing mutational process promoting cell-cell diversity, high rates of chromosomal missegregation, and consequent micronucleation. Using a novel mutation-based WGD timing method,doubleTime, we delineated specific modes by which WGD can drive tumor evolution: (i) unitary evolutionary origin followed by significant diversification, (ii) independent WGD events on a pre-existing background of copy number diversity, and (iii) evolutionarily late clonal expansions of WGD populations. Additionally, through integrated single-cell RNA sequencing and high-resolution immunofluorescence microscopy, we found that inflammatory signaling and cGAS-STING pathway activation result from ongoing chromosomal instability and are restricted to tumors that remain predominantly diploid. This contrasted with predominantly WGD tumors, which exhibited significant quiescent and immunosuppressive phenotypic states. Together, these findings establish WGD as an evolutionarily ‘active’ mutational process that promotes evolvability and dysregulated immunity in late stage ovarian cancer.

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Section: We Investigated How Chromosomal Instability Phenotypes Encod...supporting

confidence: 87%

Ongoing genome doubling promotes evolvability and immune dysregulation in ovarian cancer

McPherson,

Vázquez-García,

Myers

et al. 2024

Preprint

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“…Transient transfections were performed with Lipofectamine 2000. Luciferase activities were assayed using a luciferase reporter assay system (Promega) as previously described [ 34 , 35 ].…”

Section: Methodsmentioning

confidence: 99%

TRIB1 regulates liver regeneration by antagonizing the NRF2-mediated antioxidant response

et al. 2023

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Robust regenerative response post liver injuries facilitates the architectural and functional recovery of the liver. Intrahepatic redox homeostasis plays a key role in liver regeneration. In the present study, we investigated the contributory role of Tribbles homolog 1 (Trib1), a pseudokinase, in liver regeneration and the underlying mechanism. We report that Trib1 expression was transiently down-regulated in animal and cell models of liver regeneration. Further analysis revealed that hepatocyte growth factor (HGF) repressed Trib1 transcription by evicting liver X receptor (LXRα) from the Trib1 promoter. Knockdown of Trib1 enhanced whereas over-expression of Trib1 suppressed liver regeneration after partial hepatectomy in mice. Of interest, regulation of liver regenerative response by Trib1 coincided with alterations of intracellular ROS levels, GSH levels, and antioxidant genes. Transcriptional assays suggested that Trib1 influenced cellular redox status by attenuating nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Mechanistically, Trib1 interacted with the C-terminus of Nrf2 thus masking a potential nuclear localization signal (NLS) and blocking nuclear accumulation of Nrf2. Finally, correlation between Trib1 expression, Nrf2 nuclear localization, and cell proliferation was identified in liver specimens taken from patients with acute liver failure. In conclusion, our data unveil a novel pathway that depicts Trib1 as a critical link between intracellular redox homeostasis and cell proliferation in liver regeneration.

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“…It has widespread consequences for human health, and current research is actively exploring its molecular mechanisms. The convenient one‐flask, gram‐scale synthesis of c‐di‐GMP described here and shown in Figure 1 has facilitated these efforts and has been applied to a variety of analogs (Bartsch et al., 2022; Chen, 2023; Chen et al., 2023; Gao, Ascano, Wu, et al., 2013; Gao, Ascano, Zillinger, et al., 2013; Meehan et al., 2016; Sun et al., 2023; Yan, 2021; Zhang et al., 2013, 2023).…”

Section: Commentarymentioning

confidence: 99%

One‐Flask Synthesis of Cyclic Diguanosine Monophosphate (c‐di‐GMP)

Gaffney

Jones

2023

Current Protocols

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The bacterial signaling molecule cyclic diguanosine monophosphate (c‐di‐GMP) plays a key role in controlling biofilm formation and pathogenic virulence, among many other functions. It has widespread consequences for human health, and current research is actively exploring its molecular mechanisms. The convenient one‐flask, gram‐scale synthesis of c‐di‐GMP described here has facilitated these efforts and has been applied to a variety of analogs. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

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NF-κB regulates the expression of STING via alternative promoter usage

Cited by 5 publications

References 50 publications

Ongoing genome doubling promotes evolvability and immune dysregulation in ovarian cancer

Ongoing genome doubling promotes evolvability and immune dysregulation in ovarian cancer

TRIB1 regulates liver regeneration by antagonizing the NRF2-mediated antioxidant response

One‐Flask Synthesis of Cyclic Diguanosine Monophosphate (c‐di‐GMP)

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