N4BP3 promotes angiogenesis in hepatocellular carcinoma by binding with KAT2B

Han, Hexu; Zhu, Wenwu; Lin, Tao; Liu, Cuixia; Zhai, Hengyong

doi:10.1111/cas.15498

Cited by 11 publications

(5 citation statements)

References 33 publications

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“…Therefore, we hypothesize that KAT2B may regulate DNA damage repair through the acetylation of histones. Subsequently, we observed that H3K27ac decreased in expression after reducing KAT2B expression (Figure 6C,D), which is consistent with what others reported [41][42][43]. We also observed that the expression of BRCA2 was decreased in both KAT2B knockdown and KAT2B knockout cell lines (Figure 6C,D).…”

Section: Kat2b Affects Olaparib Sensitivity Through the Regulation Of...supporting

confidence: 90%

“…KAT2B, as a member of the BRD family, is a histone acetyltransferase and is associated with homologous recombination repair [27][28][29][30][31]. Previous reports from other laboratories have demonstrated that the acetylation induced by KAT2B significantly modulates the function of H3K27 [41][42][43]. Our present study now adds to this knowledge and shows that KAT2B knockdown and knockout affect the acetylation of H3K27 and the expression of BRCA2 (Figure 6C,D).…”

Section: Discussionsupporting

confidence: 77%

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Epigenetically Downregulated Breast Cancer Gene 2 through Acetyltransferase Lysine Acetyltransferase 2B Increases the Sensitivity of Colorectal Cancer to Olaparib

Chen,

Allgayer

2023

Cancers

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Olaparib suppresses DNA damage repair by inhibiting the poly ADP ribose polymerase (PARP), especially in cancers with BRCA1/2 mutations or the BRCA-ness phenotype. However, the first trials showed that some patients with defective DNA damage repair are still resistant to olaparib. The recovery of the wildtype BRCA is a prominent mechanism of PARP inhibitor (PARPi) resistance in BRCA-deficient tumors, but additional molecular features of olaparib resistance remain poorly understood. The objective of our study was to find molecular parameters that contribute to olaparib response or resistance in CRC. We report that histone acetyltransferase KAT2B decreases BRCA2 expression by reducing the acetylation of the 27th amino acid in histone H3 (H3K27) at the promoter of the BRCA2 gene in colorectal cancer (CRC). This increases the sensitivity of CRC cells toward olaparib treatment. The H3K27ac binding domain of BRCA2 may be required for its transcription. Low endogenous KAT2B expression, which we identify in a subset of cultured BRCA2-expressing CRC cells, leads to an accumulation of γH2AX (more DNA damage), resulting in low PARPi resistance in BRCA-expressing cells. Our results reveal KAT2B and histone acetylation as regulators of BRCA2 expression and PARPi responses in BRCA2-expressing CRC cells, providing further insights into molecular prerequisites for targeting BRCA-functional tumors.

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Section: Kat2b Affects Olaparib Sensitivity Through the Regulation Of...supporting

confidence: 90%

Section: Discussionsupporting

confidence: 77%

Epigenetically Downregulated Breast Cancer Gene 2 through Acetyltransferase Lysine Acetyltransferase 2B Increases the Sensitivity of Colorectal Cancer to Olaparib

Chen,

Allgayer

2023

Cancers

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“…Hexu Han et al found that NEDD4 binding protein 3 (N4BP3) was highly expressed in HCC, and the C-terminus of N4BP3 interacted with lysine acetyltransferase 2B (KAT2B) to regulate the distribution of the promoter of acetyl-histone H3 (Lys 27) (H3K27 ac) and increase the expression of the signal transducer and activator of transcription 3 (STAT3), thereby increasing the expression and secretion of vascular endothelial growth factor A (VEGFA) to promote angiogenesis in HCC. Furthermore, the efficacy of sorafenib was enhanced, providing a new theoretical basis for the selection of therapeutic targets in HCC [143]. Nonetheless, the exact roles of NEDD 4 and NEDD4L in HCC need to be further investigated to guide future drug research directions and identify effective diagnostic and prognostic markers for HCC to improve patients' survival (Figure 5) (Table 1).…”

Section: Nedd4/neddl and Liver Diseases 221 Nedd4/neddl And Liver Cancermentioning

confidence: 99%

NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases

Xu,

Jiang,

et al. 2024

Biomolecules

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Protein ubiquitination is an enzymatic cascade reaction and serves as an important protein post-translational modification (PTM) that is involved in the vast majority of cellular life activities. The key enzyme in the ubiquitination process is E3 ubiquitin ligase (E3), which catalyzes the binding of ubiquitin (Ub) to the protein substrate and influences substrate specificity. In recent years, the relationship between the subfamily of neuron-expressed developmental downregulation 4 (NEDD4), which belongs to the E3 ligase system, and digestive diseases has drawn widespread attention. Numerous studies have shown that NEDD4 and NEDD4L of the NEDD4 family can regulate the digestive function, as well as a series of related physiological and pathological processes, by controlling the subsequent degradation of proteins such as PTEN, c-Myc, and P21, along with substrate ubiquitination. In this article, we reviewed the appropriate functions of NEDD4 and NEDD4L in digestive diseases including cell proliferation, invasion, metastasis, chemotherapeutic drug resistance, and multiple signaling pathways, based on the currently available research evidence for the purpose of providing new ideas for the prevention and treatment of digestive diseases.

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“…Cellular extracts were meticulously prepared and subsequently analyzed through the western blotting, using appropriate antibodies, as detailed in the reference methodologies [16]. The primary antibodies used in our study included: anti-NAT10 (1:1000, 13365-1-AP, Proteintech, Wuhan, China), anti-RelA/p65 (1:1000, 8242, CST, Boston, MA, USA), anti-Flag-tag (F1804, Sigma, St. Louis, MO, USA), anti-IKba (1:1000, 4814, CST, Boston, MA, USA), anti-phospho IKba (Ser32/36) (1:1000, 9426, CST, Boston, MA, USA), anti-NF-κB p65 (Ser536) (1:1000, 3033, CST, Boston, MA, USA), anti-IKKB (1:1000, 15649-1-AP, Proteintech, Wuhan, China), anti-IKK-alpha (1:1000, GB11923, ServiceBio, Wuhan, China), and anti-β-actin (1:10,000, 66009-1-AP, Proteintech, Wuhan, China).…”

Section: Western Blotting Assaymentioning

confidence: 99%

“…Previous studies have suggested a significant involvement of the NF-κB signaling pathway in lung cancer progression [16,17]. Exploring NAT10's influence on the activation of the NF-κB signaling pathway, we used Dualluciferase reporter gene assays on our previously established stable cell lines.…”

Section: Nat10 Promotes Lung Cancer Through the Activation Of Nf-κb S...mentioning

confidence: 99%

NAT10 Promotes Malignant Progression of Lung Cancer via the NF-κB Signaling Pathway

Liu,

Zhuo

et al. 2023

Discovery Medicine

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Background: NAT10 (N-acetyltransferase 10) is a newly identified novel acetyltransferase. Abnormal expression of NAT10 is associated with several human disorders, including cancer, autoimmune diseases, and cardiovascular disease. This study aimed to investigate the role of NAT10 in promoting lung cancer malignant progression through the NF-κB (nuclear factor κB) signaling pathway. Methods: Cells lines BEAS-2B, NCI-H524, A549, PC-9, NCI-H23, and NCI-H258 were cultured for identification. Western blotting and PCR assays determined gene expression within the sample cells. Cellular functionality was assayed using CCK8 (Cell Counting Kit-8), Dual-Luciferase Reporter, and Colony formating. Results: The PCR assay and Western blotting showed a significant elevation of NAT10 levels within tumor tissues compared to paraneoplastic tissues (p < 0.05). Specifically, NAT10 only affected the expression and content of RelA/p65 in lung cancer. Analysis from the TCGA (The Cancer Genome Atlas) database indicated that elevated expression levels of NAT10 in tumors can be a good prognostic indicator for lung cancer patients. The CCK8 assay showed that the knockdown of NAT10 significantly suppressed the A549 cells' progression rate (p < 0.05). The colony formation assays further confirmed that the overexpression of NAT10 significantly increased the generation of clones in the NCI-H524 cells (p < 0.05). The proliferation rate influenced by the overexpression of NAT10 was inhibited by blocking the NF-κB signaling pathway (p < 0.05). Dual-luciferase reporter gene assay results revealed NAT10's potential in promoting the NF-κB signaling pathway's activity in lung cancer. Immunohistochemical staining underscored a strong link between NAT10 protein expression and the NF-κB signaling pathway in lung cancer tissues. Conclusions: NAT10's expression is significantly upregulated in tumor tissues, supported by PCR results. NAT10 plays a role in the development and proliferation of lung cancer cells and can activate the NF-κB signaling pathway in lung cancer. Hence, NAT10's regulation of the NF-κB signaling pathway is critical in the malignant proliferation of lung cancer.

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N4BP3 promotes angiogenesis in hepatocellular carcinoma by binding with KAT2B

Cited by 11 publications

References 33 publications

Epigenetically Downregulated Breast Cancer Gene 2 through Acetyltransferase Lysine Acetyltransferase 2B Increases the Sensitivity of Colorectal Cancer to Olaparib

Epigenetically Downregulated Breast Cancer Gene 2 through Acetyltransferase Lysine Acetyltransferase 2B Increases the Sensitivity of Colorectal Cancer to Olaparib

NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases

NAT10 Promotes Malignant Progression of Lung Cancer via the NF-κB Signaling Pathway

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