KAT6A Acetylation of SMAD3 Regulates Myeloid‐Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple‐Negative Breast Cancer

Yu, Bo; Luo, Fei; Sun, Bowen; Liu, Wenxue; Shi, Qiqi; Cheng, Shi Yuan; Chen, Ceshi; Chen, Guoqiang; Li, Yanxin; Feng, Haizhong

doi:10.1002/advs.202100014

Cited by 43 publications

(27 citation statements)

References 69 publications

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“…The analysis of the expression profile (GSE108242) obtained from the KAT6A gene knockdown model revealed that the expression of this gene was closely associated with several cancer hallmark-related pathways ( Figure 6(a) ). G2M signal checkpoint pathway (HALLMARK_G2M_CHECKPOINT) was found upregulated after the knockdown of KAT6A ( Figure 6(b) ), whereas the TGF- β signaling pathway was inhibited after KAT6A knockdown ( Figure 6(c) ); this observation was also supported by previous analysis [ 23 ].…”

Section: Resultssupporting

confidence: 86%

Genetic and Molecular Characterization Revealed the Prognosis Efficiency of Histone Acetylation in Pan-Digestive Cancers

Zhang

Wang

et al. 2022

Journal of Oncology

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The imbalance between acetylation and deacetylation of histone proteins, important for epigenetic modifications, is closely associated with various diseases, including cancer. However, knowledge regarding the modification of histones across the different types of digestive cancers is still lacking. The purpose of this research was to analyze the role of histone acetylation and deacetylation in pan-digestive cancers. We systematically characterized the molecular alterations and clinical relevance of 13 histone acetyltransferase (HAT) and 18 histone deacetylase (HDAC) genes in five types of digestive cancers, including esophageal carcinoma, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. Recurrent mutations and copy number variation (CNV) were extensively found in acetylation-associated genes across pan-digestive cancers. HDAC9 and KAT6A showed widespread copy number amplification across five pan-digestive cancers, while ESCO2, EP300, and HDAC10 had prevalent copy number deletions. Accordingly, we found that HAT and HDAC genes correlated with multiple cancer hallmark-related pathways, especially the histone modification-related pathway, PRC2 complex pathway. Furthermore, the expression pattern of HAT and HDAC genes stratified patients with clinical benefit in hepatocellular carcinoma and pancreatic cancer. These results indicated that acetylation acts as a key molecular regulation of pan-digestive tumor progression.

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Section: Resultssupporting

confidence: 86%

Genetic and Molecular Characterization Revealed the Prognosis Efficiency of Histone Acetylation in Pan-Digestive Cancers

Zhang

Wang

et al. 2022

Journal of Oncology

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“…Overexpression of YWHAE increases the proliferation, migration and invasion ability of breast cancer cells [ 18 ]. KAT6A promotes SMAD3 binding to oncogenic chromatin modifier TRIM24 and disrupts its interaction with the tumor suppressor TRIM33, which lead to the tumor cell metastasis in breast cancer [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

Predicting lymph node metastasis and prognosis of individual cancer patients based on miRNA-mediated RNA interactions

2022

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Background Lymph node metastasis is usually detected based on the images obtained from clinical examinations. Detecting lymph node metastasis from clinical examinations is a direct way of diagnosing metastasis, but the diagnosis is done after lymph node metastasis occurs. Results We developed a new method for predicting lymph node metastasis based on differential correlations of miRNA-mediated RNA interactions in cancer. The types of RNAs considered in this study include mRNAs, lncRNAs, miRNAs, and pseudogenes. We constructed cancer patient-specific networks of miRNA mediated RNA interactions and identified key miRNA–RNA pairs from the network. A prediction model using differential correlations of the miRNA–RNA pairs of a patient as features showed a much higher performance than other methods which use gene expression data. The key miRNA–RNA pairs were also powerful in predicting prognosis of an individual patient in several types of cancer. Conclusions Differential correlations of miRNA–RNA pairs identified from patient-specific networks of miRNA mediated RNA interactions are powerful in predicting lymph node metastasis in cancer patients. The key miRNA–RNA pairs were also powerful in predicting prognosis of an individual patient of solid cancer.

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“…SMAD3 is identified as a non-histone substrate of lysine acetyltransferase 6A (KAT6A). Targeting KAT6A in combination with anti-PD-L1 therapy in TNBC-bearing xenografts models reduced MDSC recruitment, significantly alleviated metastasis potential and increased overall survival ( 84 ). For advanced prostate cancer (PCa), the majority of patients are resistant to ICB, due to the accumulation of MDSCs.…”

Section: Synergistic Roles Of Icb and Targeting Mdscsmentioning

confidence: 99%

Immunotherapy of targeting MDSCs in tumor microenvironment

et al. 2022

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Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells which are abnormally accumulated during the differentiation of myeloid cells. Immunosuppression is the main functional feature of MDSCs, which inhibit T cell activity in the tumor microenvironment (TME) and promote tumoral immune escape. The main principle for immunotherapy is to modulate, restore, and remodel the plasticity and potential of immune system to have an effective anti-tumor response. In the TME, MDSCs are major obstacles to cancer immunotherapy through reducing the anti-tumor efficacy and making tumor cells more resistant to immunotherapy. Therefore, targeting MDSCs treatment becomes the priority of relevant studies and provides new immunotherapeutic strategy for cancer treatment. In this review, we mainly discuss the functions and mechanisms of MDSCs as well as their functional changes in the TME. Further, we review therapeutic effects of immunotherapy against MDSCs and potential breakthroughs regarding immunotherapy targeting MDSCs and immune checkpoint blockade (ICB) immunotherapy.

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KAT6A Acetylation of SMAD3 Regulates Myeloid‐Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple‐Negative Breast Cancer

Cited by 43 publications

References 69 publications

Genetic and Molecular Characterization Revealed the Prognosis Efficiency of Histone Acetylation in Pan-Digestive Cancers

Genetic and Molecular Characterization Revealed the Prognosis Efficiency of Histone Acetylation in Pan-Digestive Cancers

Predicting lymph node metastasis and prognosis of individual cancer patients based on miRNA-mediated RNA interactions

Immunotherapy of targeting MDSCs in tumor microenvironment

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