KAT2A succinyltransferase activity-mediated 14-3-3ζ upregulation promotes β-catenin stabilization-dependent glycolysis and proliferation of pancreatic carcinoma cells

Tong, Yuru; Guo, Dong; Dong, Yan; Ma, Chunmin; Shao, Fei; Wang, Yugang; Luo, Shudi; Lin, Liming; Tao, Jingjing; Jiang, Yuhui; Lu, Zhimin; Xing, Dongming

doi:10.1016/j.canlet.2019.09.015

Cited by 57 publications

(53 citation statements)

References 26 publications

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“…deters the combination between TLE with TCF/LEF (Perugorria et al, 2019;Tong et al, 2020). Considering that, it is interesting to explore whether miR-766-3p suppresses this pathway via BCL9L.…”

Section: Discussionmentioning

confidence: 99%

miR-766-3p Targeting BCL9L Suppressed Tumorigenesis, Epithelial-Mesenchymal Transition, and Metastasis Through the β-Catenin Signaling Pathway in Osteosarcoma Cells

Zhang

Chen

Liu

et al. 2020

Front. Cell Dev. Biol.

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Accumulating evidence has indicated that abnormal microRNAs (miRNAs) serve critical roles in carcinogenesis and development of osteosarcoma (OS). The purpose of the present study was to elucidate the relationship between miR-766-3p and development of osteosarcoma and explore the potential mechanism. In this study, we found that miR-766-3p was the most downregulated miRNA by analyzing GSE65071 from the GEO database. miR-766-3p was lowly expressed in OS tissue samples and cells, and high miR-766-3p expression repressed the malignant level of OS, including cell proliferation, EMT, migration, and invasion in vitro and in vivo. B-Cell Lymphoma 9-Like Protein (BCL9L) was negatively associated with miR-766-3p expression in OS cells and tissue samples and was validated as the downstream target by luciferase reporter assay and western blotting. Rescue experiment indicated that BCL9L could restore the influence of miR-766-3p on OS cells. In addition, the β-Catenin/TCF-4 signal pathway was demonstrated to be related to the miR-766-3p/BCL9L axis. In summary, miR-766-3p, a negative regulator of BCL9L, plays the role of tumor metastasis suppressor via the β-catenin signaling pathway in the progression of OS.

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Section: Discussionmentioning

confidence: 99%

miR-766-3p Targeting BCL9L Suppressed Tumorigenesis, Epithelial-Mesenchymal Transition, and Metastasis Through the β-Catenin Signaling Pathway in Osteosarcoma Cells

Zhang

Chen

Liu

et al. 2020

Front. Cell Dev. Biol.

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“…In contrast, KAT2A protein was overexpressed and positively correlated with tumor size in human glioma and non-small-cell lung carcinoma (NSCLC) ( Bondy-Chorney et al, 2019 ). KAT2A is also highly expressed in human pancreatic ductal adenocarcinoma (PDAC) specimens and positively correlated with advanced stages of PDAC and short patient survival ( Tong et al, 2020 ). The results of this work are consistent with these reports.…”

Section: Discussionmentioning

confidence: 99%

Gene Signature Associated With Bromodomain Genes Predicts the Prognosis of Kidney Renal Clear Cell Carcinoma

Qian

et al. 2021

Front. Genet.

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Bromodomain (BRD) proteins exhibit a variety of activities, such as histone modification, transcription factor recruitment, chromatin remodeling, and mediator or enhancer complex assembly, that affect transcription initiation and elongation. These proteins also participate in epigenetic regulation. Although specific epigenetic regulation plays an important role in the occurrence and development of cancer, the characteristics of the BRD family in renal clear cell carcinoma (KIRC) have not been determined. In this study, we investigated the expression of BRD family genes in KIRC at the transcriptome level and examined the relationship of the expression of these genes with patient overall survival. mRNA levels of tumor tissues and adjacent tissues were extracted from The Cancer Genome Atlas (TCGA) database. Seven BRD genes (KAT2A, KAT2B, SP140, BRD9, BRPF3, SMARCA2, and EP300) were searched by using LASSO Cox regression and the model with prognostic risk integration. The patients were divided into two groups: high risk and low risk. The combined analysis of these seven BRD genes showed a significant association with the high-risk groups and lower overall survival (OS). This analysis demonstrated that total survival could be predicted well in the low-risk group according to the time-dependent receiver operating characteristic (ROC) curve. The prognosis was determined to be consistent with that obtained using an independent dataset from TCGA. The relevant biological functions were identified using Gene Set Enrichment Analysis (GSEA). In summary, this study provides an optimized survival prediction model and promising data resources for further research investigating the role of the expression of BRD genes in KIRC.

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“…Furthermore, the relationship between high KAT2A expression in PDAC specimens and advanced stages of PDAC in patients is positive and associated with poor survival. In PDAC specimens, H3K79 succinylation by KAT2A in the promoter region of YWHAZ (encoding 14‐3‐3ζ) benefits YWHAZ and 14‐3‐3ζ expression, thereby restricting the degradation of β‐catenin 55 . In the presence of 14‐3‐3ζ, β‐catenin shows diminished ubiquitylation and degradation, increased stability and disassociation from the binding with β‐TrCP E3 ligase.…”

Section: The Structure and Function Of Histone Ksuc In The Nucleosomementioning

confidence: 99%

“…Moreover, 14‐3‐3ζ upregulates not only β‐catenin expression but also downstream gene expression in the cytoplasm and nucleus 56,57 . The depletion of KAT2A succinyltransferase activity by the KAT2A Y645A mutant reduces H3K79 succinylation and 14‐3‐3ζ expression, leading to harm β‐catenin stability and subsequently decreasing expression of cyclin D1, c‐Myc, GLUT1 and LDHA 55 . KAT2A‐mediated H3K79 succinylation promotes 14‐3‐3ζ and β‐catenin expression, which contributes to glycolysis, cell proliferation, migration and invasion of PDAC cells upon epithelial‐to‐mesenchymal transition 55 .…”

Section: The Structure and Function Of Histone Ksuc In The Nucleosomementioning

confidence: 99%

“…The depletion of KAT2A succinyltransferase activity by the KAT2A Y645A mutant reduces H3K79 succinylation and 14‐3‐3ζ expression, leading to harm β‐catenin stability and subsequently decreasing expression of cyclin D1, c‐Myc, GLUT1 and LDHA 55 . KAT2A‐mediated H3K79 succinylation promotes 14‐3‐3ζ and β‐catenin expression, which contributes to glycolysis, cell proliferation, migration and invasion of PDAC cells upon epithelial‐to‐mesenchymal transition 55 . These findings reveal a novel and instrumental role of KAT2A‐mediated histone succinylation in regulating gene expression and disease 55 …”

Section: The Structure and Function Of Histone Ksuc In The Nucleosomementioning

confidence: 99%

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Histone succinylation and its function on the nucleosome

Liu

Shangguan

Tang

et al. 2021

J Cellular Molecular Medi

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Protein post‐translational modifications (PTMs) of histones are ubiquitous regulatory mechanisms involved in many biological processes, including replication, transcription, DNA damage repair and ontogenesis. Recently, many short‐chain acylation histone modifications have been identified by mass spectrometry (MS). Lysine succinylation (Ksuc or Ksucc) is a newly identified histone PTM that changes the chemical environment of histones and is similar to other acylation modifications; lysine succinylation appears to accumulate at transcriptional start sites and to correlate with gene expression. Although numerous studies are ongoing, there is a lack of reviews on the Ksuc of histones. Here, we review lysine succinylation sites on histones, including the chemical characteristics and the mechanism by which lysine succinylation influences nucleosomal structure, chromatin dynamics and several diseases and then discuss lysine succinylation regulation to identify theoretical and experimental proof of Ksuc on histones and in diseases to inspire further research into histone lysine succinylation as a target of disease treatment in the future.

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KAT2A succinyltransferase activity-mediated 14-3-3ζ upregulation promotes β-catenin stabilization-dependent glycolysis and proliferation of pancreatic carcinoma cells

Cited by 57 publications

References 26 publications

miR-766-3p Targeting BCL9L Suppressed Tumorigenesis, Epithelial-Mesenchymal Transition, and Metastasis Through the β-Catenin Signaling Pathway in Osteosarcoma Cells

miR-766-3p Targeting BCL9L Suppressed Tumorigenesis, Epithelial-Mesenchymal Transition, and Metastasis Through the β-Catenin Signaling Pathway in Osteosarcoma Cells

Gene Signature Associated With Bromodomain Genes Predicts the Prognosis of Kidney Renal Clear Cell Carcinoma

Histone succinylation and its function on the nucleosome

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