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Your search keyword '"Dong, Zhexu"' showing total 3 results
Start Over Author "Dong, Zhexu" Topic basic-leucine zipper transcription factors
3 results on '"Dong, Zhexu"'

1. SARI suppresses colitis-associated cancer development by maintaining MCP-1-mediated tumour-associated macrophage recruitment.

Author

Dai L, Liu Y, Yin Y, Li J, Dong Z, Chen N, Cheng L, Wang H, Fang C, Lin Y, Shi G, Zhang H, Fan P, Su X, Zhang S, Yang Y, Yang L, Huang W, Zhou Z, Yu D, and Deng H

Subjects
Animals, Basic-Leucine Zipper Transcription Factors genetics, Basic-Leucine Zipper Transcription Factors metabolism, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic pathology, Chemokine CCL2 genetics, Colitis-Associated Neoplasms etiology, Colitis-Associated Neoplasms metabolism, Colitis-Associated Neoplasms pathology, Colonic Neoplasms etiology, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Female, Humans, Male, Mice, Mice, Knockout, Receptors, CCR2 genetics, Receptors, CCR2 metabolism, Signal Transduction, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Basic-Leucine Zipper Transcription Factors physiology, Chemokine CCL2 metabolism, Colitis complications, Colitis-Associated Neoplasms prevention & control, Colonic Neoplasms prevention & control, Inflammation physiopathology, Tumor-Associated Macrophages immunology
Abstract

SARI (suppressor of AP-1, regulated by IFN) impaired tumour growth by promoting apoptosis and inhibiting cell proliferation and tumour angiogenesis in various cancers. However, the role of SARI in regulating tumour-associated inflammation microenvironment is still elusive. In our study, the colitis-dependent and -independent primary model were established in SARI deficiency mice and immuno-reconstructive mice to investigate the functional role of SARI in regulating tumour-associated inflammation microenvironment and primary colon cancer formation. The results have shown that SARI deficiency promotes colitis-associated cancer (CAC) development only in the presence of colon inflammation. SARI inhibited tumour-associated macrophages (TAM) infiltration in colon tissues, and SARI deficiency in bone marrow cells has no observed role in the promotion of intestinal tumorigenesis. Mechanism investigations indicated that SARI down-regulates p-STAT1 and STAT1 expression in colon cancer cells, following inhibition of MCP-1/CCR2 axis activation during CAC development. Inverse correlations between SARI expression and macrophage infiltration, MCP-1 expression and p-STAT1 expression were also demonstrated in colon malignant tissues. Collectively, our results prove the inhibition role of SARI in colon cancer formation through regulating TAM infiltration., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Published
2020
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2. SARI attenuates colon inflammation by promoting STAT1 degradation in intestinal epithelial cells.

Author

Dai L, Liu Y, Cheng L, Wang H, Lin Y, Shi G, Dong Z, Li J, Fan P, Wang Q, Su X, Zhang S, Yang Y, Hu X, Huang W, Zhou Z, Yu D, Probert C, Wei Y, and Deng H

Subjects
Animals, Basic-Leucine Zipper Transcription Factors metabolism, Biomarkers, Colitis diagnostic imaging, Colitis pathology, Colonoscopes, Disease Models, Animal, Immunohistochemistry, Intestinal Mucosa pathology, Leukocytes immunology, Leukocytes metabolism, Leukocytes pathology, Mice, Mice, Knockout, Proteolysis, Receptors, CCR2 genetics, Basic-Leucine Zipper Transcription Factors genetics, Colitis etiology, Colitis metabolism, Epithelial Cells metabolism, Intestinal Mucosa metabolism, STAT1 Transcription Factor metabolism
Abstract

SARI functions as a suppressor of colon cancer and predicts survival of colon cancer patients, but its role in regulating colitis has not been characterized. Here we show that SARI -/- mice were highly susceptible to colitis, which was associated with enhanced macrophage infiltration and inflammatory cytokine production. Bone marrow reconstitution experiments demonstrated that disease susceptibility was not dependent on the deficiency of SARI in the immune compartment but on the protective role of SARI in the intestinal epithelial cells (IECs). Furthermore, SARI deficiency enhanced Chemokine (C-C motif) Ligand 2 (CCL2) production and knockout of CCR2 blocks the promoting role of SARI deficiency on colitis. Mechanistically, SARI directly targets and promotes signal transducer and activator of transcription 1 (STAT1) degradation in IECs, followed by persistent inactivation of the STAT1/CCL2 transcription complex. In summary, SARI attenuated colitis in mice by impairing colitis-dependent STAT1/CCL2 transcriptional activation in IECs and macrophages recruitment in colon tissue.

Published
2019
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3. Targeted demethylation of the SARI promotor impairs colon tumour growth.

Author

Wang Q, Dai L, Wang Y, Deng J, Lin Y, Wang Q, Fang C, Ma Z, Wang H, Shi G, Cheng L, Liu Y, Chen S, Li J, Dong Z, Su X, Yang L, Zhang S, Jiang M, Huang M, Yang Y, Yu D, Zhou Z, Wei Y, and Deng H

Subjects
Animals, Basic-Leucine Zipper Transcription Factors metabolism, Cell Line, Tumor, Cell Movement, Cell Proliferation, Colonic Neoplasms metabolism, DNA Methylation drug effects, Down-Regulation, Humans, Mice, Mice, Inbred BALB C, Tumor Suppressor Proteins metabolism, Basic-Leucine Zipper Transcription Factors physiology, Colonic Neoplasms drug therapy, DNA Methylation physiology, Promoter Regions, Genetic physiology, Tumor Suppressor Proteins physiology
Abstract

SARI (suppressor of activator protein 1, regulated by IFN) functions as a tumour suppressor and is inactivated in various cancers. However, the mechanism underlying SARI inactivation in cancer remains elusive. In this study, we detected a high level of DNA methylation of the SARI promoter and an inverse correlation between SARI promoter methylation and expression in malignant tissues from patients with colon cancer. Furthermore, we found that the SARI promoter methylation status is a prognostic indicator for patients with colon cancer. A dCas9-multiGCN4/scFv-TET1CD-sgRNA-based SARI-targeted demethylation system (dCas9-multiGCN4/scFv-TET1CD-sgSARI) was constructed to precisely and specifically demethylate regions of SARI; this system resulted in the substantial activation of SARI expression. Further in vitro and in vivo data confirmed that dCas9-multiGCN4/scFv-TET1CD-sgSARI exerts anti-tumour effects by regulating tumour proliferation, apoptosis, and angiogenesis. Collectively, specific demethylation of the SARI promoter and restoration of endogenous SARI expression by dCas9-multiGCN4/scFv-TET1CD-SARI have therapeutic applications for colon cancer and perhaps for other cancers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Published
2019
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