The NOTCH4-GATA4-IRG1 axis as a novel target in early-onset colorectal cancer

Scheurlen, Katharina M.; Chariker, Julia H.; Kanaan, Ziad; Littlefield, Andrew B.; George, Joan B.; Seraphine, Caden; Rochet, Andre; Rouchka, Eric C.; Galandiuk, Susan

doi:10.1016/j.cytogfr.2022.06.002

Cited by 18 publications

(9 citation statements)

References 97 publications

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“…Past studies identified GATA4’s inhibitory influence on hepatocellular carcinoma, colorectal cancer, and lung cancer via the modulation of pathways like Wnt/β-catenin [ 36 ], NOTCH/IRG1 [ 41 ] and TGFβ [ 42 ], while GATA4 acts as a cancer booster on acute lymphocytic leukemia by MDM2/p53 pathway. Our research revealed the inhibitory effect on breast cancer of GATA4 via NF-κB pathway.…”

Section: Discussionmentioning

confidence: 99%

GATA4 regulates the transcription of MMP9 to suppress the invasion and migration of breast cancer cells via HDAC1-mediated p65 deacetylation

Yang,

Song,

et al. 2024

Cell Death Dis

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GATA-binding protein 4 (GATA4) is recognized for its significant roles in embryogenesis and various cancers. Through bioinformatics and clinical data, it appears that GATA4 plays a role in breast cancer development. Yet, the specific roles and mechanisms of GATA4 in breast cancer progression remain elusive. In this study, we identify GATA4 as a tumor suppressor in the invasion and migration of breast cancer. Functionally, GATA4 significantly reduces the transcription of MMP9. On a mechanistic level, GATA4 diminishes MMP9 transcription by interacting with p65 at the NF-κB binding site on the MMP9 promoter. Additionally, GATA4 promotes the recruitment of HDAC1, amplifying the bond between p65 and HDAC1. This leads to decreased acetylation of p65, thus inhibiting p65’s transcriptional activity on the MMP9 promoter. Moreover, GATA4 hampers the metastasis of breast cancer in vivo mouse model. In summary, our research unveils a novel mechanism wherein GATA4 curtails breast cancer cell metastasis by downregulating MMP9 expression, suggesting a potential therapeutic avenue for breast cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

GATA4 regulates the transcription of MMP9 to suppress the invasion and migration of breast cancer cells via HDAC1-mediated p65 deacetylation

Yang,

Song,

et al. 2024

Cell Death Dis

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“…As a member of the GATA family, GATA4 is reported to be required in cancer [54], and it may also play a role in AKI. GATA4 can affect the progression of liver fibrosis by regulating the expression levels of fibrogenic and anti-fibrotic genes in hepatic stellate cells [55], and it can also co-operate with other signaling pathways, such as Notch signaling and PI3K/AKT signaling, as a potential therapeutic target for tumor diseases [56]. As another member of the GATA protein family, GATA3 has been validated to be expressed in many tumors (breast cancer, renal tumor, and endocrine tumor), and can be used as a diagnostic or prognostic indicator of tumor diseases [57].…”

Section: Discussionmentioning

confidence: 99%

Screening Differential Expression Profiles of Urinary microRNAs in a Gentamycin-Induced Acute Kidney Injury Canine Model

Sun

Chen

et al. 2023

Kidney and Dialysis

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microRNAs (miRNAs) are promising biomarkers for different pathological models because of their stable and detectable characters in biofluids. Here, we collected urine samples from 5 beagle dogs on the 3th, 6th, and 12th day in an acute kidney injury (AKI) caused by gentamycin. miRNA levels were measured with high-throughput sequencing and the results were then differentially investigated. Gene Ontology (GO) and KEGG pathway analysis were performed to analyze potential target genes corresponding to the differentially expressed miRNAs (DE-miRNAs). Relationships between hub genes and DE-miRNAs were analyzed with STRING and Cytoscape. We identified 234 DE-miRNAs 3, 6, and 12 days after gentamycin treatment (p < 0.05). Top 10 up- and down-regulated candidate target genes of DE-miRNAs were predicted by overlapping TargetScan and miRanda results). GO and KEGG analyses for DE-miRNAs demonstrated that the DE-miRNAs target genes are mainly involved in kidney injury-related pathways, such as the insulin signaling pathway, oxytocin signaling pathway, and hedgehog signaling pathway. The network of miRNA-hub genes suggests that miR-452, miR-106a, and 106b participate in regulating the largest number of hub genes. We evaluated the miRNA signature via a canine model built by gentamycin-caused acute kidney injury. Our results represent a valuable resource for evaluating miRNAs as biomarkers of renal toxicity.

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“…[ 36 ] PI3K/AKT activation in CRC could lead to increasing cell survival, hyperplasia, and cell proliferation. [ 37 ] Target to PI3K/AKT signaling pathway could contribute to improve therapeutic effect in CRC. [ 18 , 38 ] And most importantly, Wnt, PI3K-Akt and NF-κB signaling pathways might associate with tumor immune microenvironment in CRC.…”

Section: Discussionmentioning

confidence: 99%

NIFK as a potential prognostic biomarker in colorectal cancer correlating with immune infiltrates

Tan,

He,

et al. 2023

Medicine

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Background: Immune-related initiation, progress, metastasis and sensitivity to treatment associated with poor prognosis of patients with colorectal cancer (CRC). The role of Nucleolar protein interacting with the FHA domain of MKI67 (NIFK) in CRC remained to be investigated. We explore whether NIFK correlates with tumor immune infiltration and plays an important role in CRC patient prognosis. Methods: The data of samples involved in our study was obtained from TCGA and GEO and samples for protein expression detection and clinical information analysis were obtained from our hospital. NIFK expression, association with patient prognosis, correlation with infiltration of immune cells and its correlated genes involved in signaling pathways were analyzed using bioinformatics method along with experimental validation and clinical correlation analysis. Results: Results indicated that the expression of NIFK in tumor tissues was significantly increased compared with normal samples. colon and rectal cancer patients with high NIFK expression have poor survival compared with those with low NIFK expression. Results of cell experiments indicated that NIFK is positively correlated with cell proliferation and migration in CRC. NIFK negatively correlated with T cell CD8+, Tregs, Neutrophil and macrophage significantly. DARS and NKRF were positively correlated with NIFK and DARS correlated with CD8 + T cell, CD4 + T cell, macrophage and Neutrophil, NKRF correlated with CD8 + T cell, CD4 + T cell and macrophage in colon and rectal cancer. NIFK along with its correlated genes as DARS and NKRF were involved in Wnt, PI3K-Akt, NF-κB signaling and Intestinal immune network for lgA production. Conclusions: Our results suggested that NIFK might be a biomarker associated with poor prognosis of CRC patients, and it would be a potential target for CRC therapy.

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The NOTCH4-GATA4-IRG1 axis as a novel target in early-onset colorectal cancer

Cited by 18 publications

References 97 publications

GATA4 regulates the transcription of MMP9 to suppress the invasion and migration of breast cancer cells via HDAC1-mediated p65 deacetylation

GATA4 regulates the transcription of MMP9 to suppress the invasion and migration of breast cancer cells via HDAC1-mediated p65 deacetylation

Screening Differential Expression Profiles of Urinary microRNAs in a Gentamycin-Induced Acute Kidney Injury Canine Model

NIFK as a potential prognostic biomarker in colorectal cancer correlating with immune infiltrates

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