A Positive Feedback Loop Between Gastric Cancer Cells and Tumor-associated Macrophage Induces Malignancy Progression

Abstract Background: Hypoxia and inflammation tumor microenvironment (TME) play a crucial role in tumor development and progression. Although increased understanding of TME contributed to gastric cancer (GC) progression and prognosis, the direct interaction between macrophage and GC cells was not fully understood.Methods: Hypoxia and normoxia macrophage microarrays of GEO database was analyzed. The peripheral blood mononuclear cell acquired from the healthy volunteers. The expression of CXCL8 in GC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR), western-blot, Elisa and immunofluorescence. Cell proliferation, migration, and invasion were evaluated by cell counting kit 8 (CCK8), colony formation, real-time imaging of cell migration and transwell. Luciferase reporter assays and chromatin immunoprecipitation were used to identify the interaction between transcription factor and target gene. Especially, a series of truncated and mutation reporter genes were applied to identify precise binding sites.The corresponding functions were verified in the complementation test and in vivo animal experiment.Results: Our results revealed that Hypoxia triggered macrophage secreted C-X-C Motif Chemokine Ligand 8 (CXCL8), which induced GC invasion and proliferation. This macrophage-induced GC progression was CXCL8 activated C-X-C Motif Chemokine Receptor 1/2 (CXCR1/2) on the GC cell membrane subsequently hyperactivated Janus kinase 1/ Signal transducer and activator of transcription 1 (JAK/STAT1) signaling pathway. Then, the transcription factor STAT1 directly led to the overexpression and secretion of Interleukin 10 (IL-10). Correspondingly, IL-10 induced the M2-type polarization of macrophages through the Nuclear Factor kappa B (NF-κB) pathway-dependent mechanism and continued to increase the expression and secretion of CXCL8 through the transcription factor Nuclear Factor Kappa B Subunit 1 (NFKB1, p50). It suggested a positive feedback loop between macrophage and GC. In clinical GC samples, increased CXCL8 predicted a patient's pessimistic outcome.Conclusion: Our work identified a positive feedback loop governing cancer cells and macrophage in GC that contributed to tumor progression and patient outcome.

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Estrogen Receptor Beta Inhibits The Proliferation, Migration, And Angiogenesis Of Gastric Cancer Cells Through Inhibiting Nuclear Factor-Kappa B Signaling

OncoTargets and Therapy ◽

10.2147/ott.s214529 ◽

2019 ◽

Vol Volume 12 ◽

pp. 9153-9164

Author(s):

Yiping Zhang ◽

Yahua Wu ◽

Xufeng Zhou ◽

Benyi Yi ◽

Lili Wang

Keyword(s):

Gastric Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Nuclear Factor Kappa B ◽

Estrogen Receptor Beta ◽

Nuclear Factor ◽

Gastric Cancer Cells ◽

Nuclear Factor Kappa ◽

Receptor Beta

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Estrogen Receptor Beta Inhibits the Proliferation, Migration, and Angiogenesis of Gastric Cancer Cells Through Inhibiting Nuclear Factor-Kappa B Signaling [Retraction]

OncoTargets and Therapy ◽

10.2147/ott.s270074 ◽

2020 ◽

Vol Volume 13 ◽

pp. 6853-6854

Author(s):

Yiping Zhang ◽

Yahua Wu ◽

Xufeng Zhou ◽

Benyi Yi ◽

Lili Wang

Keyword(s):

Gastric Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Nuclear Factor Kappa B ◽

Estrogen Receptor Beta ◽

Nuclear Factor ◽

Gastric Cancer Cells ◽

Nuclear Factor Kappa ◽

Receptor Beta

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Da0324, an inhibitor of nuclear factor-κB activation, demonstrates selective antitumor activity on human gastric cancer cells

Drug Design Development and Therapy ◽

10.2147/dddt.s90081 ◽

2016 ◽

pp. 979 ◽

Cited By ~ 1

Author(s):

Jianzhang Wu ◽

Rong Jin ◽

Yiqun Xia ◽

Qiuxiang Chen ◽

Wulan Li ◽

...

Keyword(s):

Gastric Cancer ◽

Antitumor Activity ◽

Cancer Cells ◽

Nuclear Factor Kappa B ◽

Human Gastric Cancer ◽

Nuclear Factor ◽

Gastric Cancer Cells ◽

Nuclear Factor Kappa

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The interplay between ATF2 and NEAT1 contributes to lung adenocarcinoma progression

Cancer Cell International ◽

10.1186/s12935-020-01697-8 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Jian Liu ◽

Kai Li ◽

Rui Wang ◽

Sisi Chen ◽

Jie Wu ◽

...

Keyword(s):

Cell Proliferation ◽

Transcription Factor ◽

Lung Adenocarcinoma ◽

Positive Feedback ◽

Feedback Loop ◽

Tumor Model ◽

Luciferase Reporter ◽

Activator Protein 1 ◽

Positive Feedback Loop ◽

Rna Immunoprecipitation

Abstract Background Activating transcription factor 2 (ATF2), a member of the activator protein 1 (AP-1) transcription factor family, has been shown to be involved in the pathobiology of numerous cancers. However, the biological role and mechanism of ATF2 in lung adenocarcinoma (LUAD) remains to be elucidated. Methods The expression of ATF2, NEAT1 and miR-26a-5p in LUAD tissues and cell lines was detected by qRT-PCR and western blotting. The interaction between ATF2, NEAT1, and miR-26a-5p was validated by chromatin immunoprecipitation, luciferase reporter assay and RNA immunoprecipitation. Cell proliferation, invasion and tumorigenesis of LUAD cells were analyzed by using CCK8, transwell invasion assay and xenograft tumor model. Results We confirmed that ATF2 expression was increased in LUAD tissues compared with normal adjacent lung tissues. Functional experiments showed that ATF2 positively regulated cell proliferation and invasion in LUAD cells. Moreover, we identified that NEAT1 expression was increased in LUAD tissues and positively correlated with ATF2 expression. Mechanistically, ATF2 could bind to the promoter of NEAT1 to promote its transcription. Rescue experiments showed that ATF2 exerted its oncogenic function in LUAD, at least, partly through NEAT1 upregulation. In turn, NEAT1 could positively regulate ATF2 expression and form a positive feedback loop in LUAD cells. Furthermore, we demonstrated that NEAT1 positively regulated ATF2 expression via sponging miR-26a-5p. Conclusion ATF2 and NEAT1 form a positive feedback loop mediated by miR-26a-5p and coordinately contribute to LUAD progression.

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C-MYC inducible onco-lncRNA LINC00036 acting as EGFR mRNA stabilizer via RNA-protein and RNA-RNA interactions decreases the sensitivity of gefitinib in human cancer

10.21203/rs.3.rs-240846/v1 ◽

2021 ◽

Author(s):

Shouping Xu ◽

Lin Wan ◽

Qin Wang ◽

Huizi Yin ◽

Kun Qiao ◽

...

Keyword(s):

Cancer Cells ◽

Molecular Mechanism ◽

Positive Feedback ◽

Feedback Loop ◽

Human Cancer ◽

Luciferase Reporter ◽

Positive Feedback Loop ◽

Different Types

Abstract Background: The oncogenic lncRNA based strategies for combating cancer may usher in a new and promising paradigm in cancer therapy. However, few studies have been performed to solve such a critical issue. The complex traits and molecular mechanism of such lncRNAs in tumorigenesis and their relationship with sensitivity of gefitinib in human cancer have not been investigated.Methods: We aimed to identify and validate such a novel oncogenic LINC00036 using transcriptome sequencing approach and a large number of tissue samples of different types of cancer from the our cancer center cohort and public data cohorts from the Cancer Genome Atlas，Gene Expression Omnibus and Cancer Cell Line Encyclopedia. Moreover, series of in vitro and in vivo experiments were performed to examine its roles in tumorigenesis and the sensitivity of gefitinib in different types of cancer cells. Special nanoparticle via a more potent delivery system was developed to investigate the feasibility of targeting LINC00036 in vivo. Furthermore, chromatin immunoprecipitation (ChIP)-sequencing, ChIP, actinomycin D assay, dual-luciferase reporter assay, RNA pull-down and RNA immunoprecipitation were performed were developed to uncover the molecular mechanism.Results: LINC00036 that associated with poor prognosis is significantly upregulated in human cancer tissues. Series of in vitro and in vivo experiments reveal that LINC00036 promotes tumorigenesis and decreases the sensitivity of gefitinib in different types of cancer cells. LINC00036 targeting nanoparticle markedly reduced the growth of human cancer xenografts. Mechanistically, LINC00036 is a direct transcriptional target of c-MYC and a positive feedback loop of the c-MYC-LINC00036-EGFR axis exists in human cancer. LINC00036 acts as an EGFR mRNA stabilizer via RNA-protein and RNA-RNA interactions, inducing the hyper-activation of the downstream AKT and MAPK signaling pathways, which in turn decreases the sensitivity of gefitinib in human cancer.Conclusions: LINC00036, a c-MYC inducible onco-lncRNA, acts an oncogene in human cancer and decreases the sensitivity of gefitinib through positive feedback loop of the c-MYC-LINC00036-EGFR axis. Overall, this study broadens knowledge regarding novel onco-lncRNAs and will assist in developing feasible onco-lncRNAs based-targeted therapeutic strategies to improve the sensitivity of gefitinib in human cancer.

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Acquisition of resistance to trastuzumab in gastric cancer cells is associated with activation of IL-6/STAT3/Jagged-1/Notch positive feedback loop

Oncotarget ◽

10.18632/oncotarget.3241 ◽

2014 ◽

Vol 6 (7) ◽

pp. 5072-5087 ◽

Cited By ~ 53

Author(s):

Zhengyan Yang ◽

Liang Guo ◽

Dan Liu ◽

Limin Sun ◽

Hongyu Chen ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Positive Feedback ◽

Feedback Loop ◽

Gastric Cancer Cells ◽

Positive Feedback Loop

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Challenges with Methods for Detecting and Studying the Transcription Factor Nuclear Factor Kappa B (NF-κB) in the Central Nervous System

Cells ◽

10.3390/cells10061335 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1335

Author(s):

Marina Mostafizar ◽

Claudia Cortes-Pérez ◽

Wanda Snow ◽

Jelena Djordjevic ◽

Aida Adlimoghaddam ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Signaling Pathways ◽

Quantitative Methods ◽

Nuclear Factor Kappa B ◽

Inflammatory Responses ◽

Nuclear Factor ◽

Nuclear Factor Kappa ◽

Regulated Gene Expression ◽

Transcription Factor Nuclear Factor

The transcription factor nuclear factor kappa B (NF-κB) is highly expressed in almost all types of cells. NF-κB is involved in many complex biological processes, in particular in immunity. The activation of the NF-κB signaling pathways is also associated with cancer, diabetes, neurological disorders and even memory. Hence, NF-κB is a central factor for understanding not only fundamental biological presence but also pathogenesis, and has been the subject of intense study in these contexts. Under healthy physiological conditions, the NF-κB pathway promotes synapse growth and synaptic plasticity in neurons, while in glia, NF-κB signaling can promote pro-inflammatory responses to injury. In addition, NF-κB promotes the maintenance and maturation of B cells regulating gene expression in a majority of diverse signaling pathways. Given this, the protein plays a predominant role in activating the mammalian immune system, where NF-κB-regulated gene expression targets processes of inflammation and host defense. Thus, an understanding of the methodological issues around its detection for localization, quantification, and mechanistic insights should have a broad interest across the molecular neuroscience community. In this review, we summarize the available methods for the proper detection and analysis of NF-κB among various brain tissues, cell types, and subcellular compartments, using both qualitative and quantitative methods. We also summarize the flexibility and performance of these experimental methods for the detection of the protein, accurate quantification in different samples, and the experimental challenges in this regard, as well as suggestions to overcome common challenges.

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