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.202105793

Cited by 9 publications

(12 citation statements)

References 33 publications

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“…The online PROMO database showed that SMAD3 was a transcription factor binding to the SEAS1 promoter. Moreover, Yu et al [ 41 ] reported that SMAD3 acted as an oncogene in TNBC through the KAT6A acetylation-dependent regulatory mechanism. In conclusion, our data demonstrated a relationship between SMAD3, SEAS1, and miR-3940-3p in TNBC cells.…”

Section: Discussionmentioning

confidence: 99%

LncRNA SEMA3B-AS1 inhibits breast cancer progression by targeting miR-3940/KLLN axis

Huang

et al. 2022

Cell Death Dis

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Long noncoding RNAs (lncRNAs) play crucial regulatory roles in the progression of various cancers. However, the functional roles of lncRNAs in breast cancer remain unclear. In this study, we investigated the functional role of a novel long noncoding RNA SEMA3B-AS1 (lncRNA SEAS1) in breast cancer progression and the underlying mechanisms. SEAS1 was downregulated in the triple-negative breast cancer (TNBC) tissues compared with the para-carcinoma tissues, which was associated with poor prognosis of TNBC patients. We demonstrated that SEAS1 knockdown significantly increased the proliferation, migration, and invasion of TNBC cell lines, whereas SEAS1 overexpression reversed these effects. Bioinformatics analysis demonstrated that microRNA (miR)-3940-3p was a potential target of SEAS1. Mechanistically, RNA immunoprecipitation (RIP) and luciferase reporter assays confirmed that lncRNA SEMA3B-AS1 acted as sponge for miR-3940-3p, preventing the degradation of its target gene KLLN, which acts as a tumor-inhibiter in TNBC. Moreover, RNA pulldown, mass spectrometry, ChIP, and luciferase reporter assays confirmed that SMAD3 directly interacted with the promoter of SEAS1 and suppressed its transcription, thereby promoting TNBC progression. The clinical samples of TNBC confirmed SEAS1 was correlated inversely with lymphatic and distant metastasis. In conclusion, our findings reveal a novel pathway for TNBC progression via SMAD3/lncRNA SEAS1/miR-3940-3p/KLLN axis, and suggest that SEAS1 may serve as a potential biomarker and therapeutic target for TNBC.

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Section: Discussionmentioning

confidence: 99%

LncRNA SEMA3B-AS1 inhibits breast cancer progression by targeting miR-3940/KLLN axis

Huang

et al. 2022

Cell Death Dis

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“…KAT6A is also involved in triple-negative breast cancer, ovarian cancer and haematological malignancies. 2,6,19 Research has demonstrated that 51% of patients with KAT6A syndrome that have nonsense mutations also have cardiac malformations. 11 This is similar to the current case as he had ASD.…”

Section: Discussionmentioning

confidence: 99%

“… 1 It is associated with several tumours and biological processes such as leukaemia, triple-negative breast cancer, leukaemia cell proliferation, tumorigenicity and chemoresistance via acetylation epigenetics. 2 – 6 KAT6A protein may regulate gene transcription and a large number of protein modifications because of its modifiable lysine residues. 6 KAT6A protein plays an important role in development.…”

Section: Introductionmentioning

confidence: 99%

“… 2 – 6 KAT6A protein may regulate gene transcription and a large number of protein modifications because of its modifiable lysine residues. 6 KAT6A protein plays an important role in development. 7 KAT6A gene knockout mice show embryonic lethality and homozygous deletion of KAT6A in mice results in high penetrance of ventricular septal defects.…”

Section: Introductionmentioning

confidence: 99%

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The clinical spectrum of a nonsense mutation in KAT6A: a case report

Wang

et al. 2022

J Int Med Res

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KAT6A syndrome is an autosomal dominant genetic disorder associated with intellectual disability due to mutations in the lysine acetyltransferase 6A ( KAT6A) gene. There are some differences in phenotype between KAT6A gene variants. This current case report describes a 1-month-old male infant that had a nonsense mutation in the KAT6A gene. Neither of his parents had the mutation. The proband had feeding difficulties and a physical examination revealed the following: moderate dysphagia, hypoplastic laryngeal cartilage, poor audio-visual response, poor head-up ability, no active grasping awareness, microcephaly, high arched palate and he was significantly behind other children of the same age. Echocardiography showed that the foramen ovale was not closed. He was diagnosed with atrial septal defect (ASD) when 2 years old. The patient received ASD repair at 32 months of age. Head colour Doppler ultrasonography and brain magnetic resonance imaging showed cysts in the right ventricle and choroid plexus, which returned to normal at 2 years of age. This current case demonstrates that immediate surgery should be considered in newborns with KAT6A syndrome presenting with a heart malformation. A new KAT6A syndrome phenotype is described in this current case report, which requires early diagnosis and treatment.

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“…3b). 139 Immune cell protein acetylation in shaping of antitumor immune responses: Protein acetylation in immune cells also regulates tumor-killing activity. STAT6 acetylation in TAMs affects their polarization and tumor-killing ability.…”

Section: Protein Acylation In Human Diseases Acetylation and Its Role...mentioning

confidence: 99%

Protein acylation: mechanisms, biological functions and therapeutic targets

Shang

Liu

Hua

2022

Sig Transduct Target Ther

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Metabolic reprogramming is involved in the pathogenesis of not only cancers but also neurodegenerative diseases, cardiovascular diseases, and infectious diseases. With the progress of metabonomics and proteomics, metabolites have been found to affect protein acylations through providing acyl groups or changing the activities of acyltransferases or deacylases. Reciprocally, protein acylation is involved in key cellular processes relevant to physiology and diseases, such as protein stability, protein subcellular localization, enzyme activity, transcriptional activity, protein–protein interactions and protein–DNA interactions. Herein, we summarize the functional diversity and mechanisms of eight kinds of nonhistone protein acylations in the physiological processes and progression of several diseases. We also highlight the recent progress in the development of inhibitors for acyltransferase, deacylase, and acylation reader proteins for their potential applications in drug discovery.

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

Cited by 9 publications

References 33 publications

LncRNA SEMA3B-AS1 inhibits breast cancer progression by targeting miR-3940/KLLN axis

LncRNA SEMA3B-AS1 inhibits breast cancer progression by targeting miR-3940/KLLN axis

The clinical spectrum of a nonsense mutation in KAT6A: a case report

Protein acylation: mechanisms, biological functions and therapeutic targets

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