HBO1 induces histone acetylation and is important for non-small cell lung cancer cell growth

Chen, Tengfei; Hao, Huifei; Zhang, Yan; Chen, Xiaoyu; Zhao, Huasi; Yang, Rui; Li, Ping; Qiu, Lingxiao; Sang, Yonghua; Xu, Chun; Liu, Shao-Xia

doi:10.7150/ijbs.72526

Cited by 21 publications

(17 citation statements)

References 52 publications

(86 reference statements)

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“…Western blotting, real-time quantitative reverse transcription PCR (qRT-PCR), nuclear EdU (5-Ethynyl-2′- deoxyuridine)/DAPI (4′,6-diamidino2-phenylindole) staining (testing cell proliferation), nuclear TUNEL (TdT-mediated dUTP Nick-End Labeling)/DAPI staining, propidium iodide (PI)-flow cytometry (testing cell cycle progression), “Transwell” assays (testing in vitro cell migration) and Caspase-3/−9 activity assays were described in other studies [ 20 , 27 – 30 ]. Figure S1 listed the uncropped blotting images.…”

Section: Methodsmentioning

confidence: 99%

“…HBO1 also binds to different subunits and cofactors, important in gene transcription and regulating multiple physiological functions and behaviors [ 14 – 19 ]. Recent studies have established an important role of HBO1 in the development and progression of multiple malignancies [ 14 , 20 – 24 ]. Inactivation, silencing, or depletion of HBO1 could result in robust anti-cancer activity [ 14 , 20 – 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have established an important role of HBO1 in the development and progression of multiple malignancies [ 14 , 20 – 24 ]. Inactivation, silencing, or depletion of HBO1 could result in robust anti-cancer activity [ 14 , 20 – 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…WM-3835 is a first-in-class HBO1 inhibitor that hinders Histone H3/H4 acetylation and downregulates multiple genes that are closely associated with cancer progression [ 20 , 25 ]. The results of this study will show that HBO1 inactivation by WM-3835 robustly inhibits primary CRPC cell growth in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

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A first-in-class HBO1 inhibitor WM-3835 inhibits castration-resistant prostate cancer cell growth in vitro and in vivo

Zhang

et al. 2023

Cell Death Dis

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The prognosis and overall survival of castration-resistant prostate cancer (CRPC) patients are poor. The search for novel and efficient anti-CRPC agents is therefore extremely important. WM-3835 is a cell-permeable, potent and first-in-class HBO1 (KAT7 or MYST2) inhibitor. Here in primary human prostate cancer cells-derived from CRPC patients, WM-3835 potently inhibited cell viability, proliferation, cell cycle progression and in vitro cell migration. The HBO1 inhibitor provoked apoptosis in the prostate cancer cells. It failed to induce significant cytotoxicity and apoptosis in primary human prostate epithelial cells. shRNA-induced silencing of HBO1 resulted in robust anti-prostate cancer cell activity as well, and adding WM-3835 failed to induce further cytotoxicity in the primary prostate cancer cells. Conversely, ectopic overexpression of HBO1 further augmented primary prostate cancer cell proliferation and migration. WM-3835 inhibited H3-H4 acetylation and downregulated several pro-cancerous genes (CCR2, MYLK, VEGFR2, and OCIAD2) in primary CRPC cells. Importantly, HBO1 mRNA and protein levels are significantly elevated in CRPC tissues and cells. In vivo, daily intraperitoneal injection of WM-3835 potently inhibited pPC-1 xenograft growth in nude mice, and no apparent toxicities detected. Moreover, intratumoral injection of HBO1 shRNA adeno-associated virus (AAV) suppressed the growth of primary prostate cancer xenografts in nude mice. H3-H4 histone acetylation and HBO1-dependent genes (CCR2, MYLK, VEGFR2, and OCIAD2) were remarkably decreased in WM-3835-treated or HBO1-silenced xenograft tissues. Together, targeting HBO1 by WM-3835 robustly inhibits CRPC cell growth.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A first-in-class HBO1 inhibitor WM-3835 inhibits castration-resistant prostate cancer cell growth in vitro and in vivo

Zhang

et al. 2023

Cell Death Dis

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“…The importance of histone acetylation has been confirmed in cancer; it regulates gene transcription and cellular processes such as immune response, apoptosis, autophagy, tumor mutational burden (TMB), cell cycle arrest, DNA damage repair, and metabolism (8). Abnormal histone acetylation is a hallmark of many cancers, particularly NSCLC (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Histone acetylation modification regulator-mediated tumor microenvironment infiltration characteristics and prognostic model of lung adenocarcinoma patients

Wang¹,

Shen²,

Zhang³

et al. 2022

J Thorac Dis

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Background: The incidence rate of lung adenocarcinoma (LUAD) is rapidly increasing. Recent studies have reported that histone acetylation modification plays an important role in the occurrence and development of tumors. However, the potential role of modification of histone acetylation modification in the development of tumor immune microenvironment is still unclear.Methods: In this study, we comprehensively evaluated the acetylation modification patterns of LUAD samples obtained from various different databases based on 36 histone modification regulators, and constructed a prognostic model based on The Cancer Genome Atlas (TCGA) LUAD cohort using the Cox regression method. The close relationship between histone acetylation and tumor immune characteristics was further studied, including immune infiltration, immune escape and immunotherapy. Finally, we combined three cohort (GSE30219, GSE72094 and GSE50081) from Gene Expression Omnibus (GEO) database to verify the above results.Results: We analyzed the expression, mutation and interaction of 36 histone acetylation regulated genes.After Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO), 5 genes (KAT2B, SIRT2, HDAC5, KAT8, HDAC2) were screened to establish the prognosis model and calculate the risk score. Then, patients in the TCGA cohort were divided into high-and lowrisk groups based on the risk scores. Further analysis indicated that patients in the high-risk group exhibited significantly reduced overall survival (OS) compared with those in the low-risk group. The high-and lowrisk groups exhibited significant differences in terms of tumor immune characteristics, such as immune infiltration, immune escape and immunotherapy. The high-risk group had lower immune score, less immune cell infiltration and higher clinical stage. Moreover, multivariate analysis revealed that this prognostic model might be a powerful prognostic predictor for LUAD. In addition, drugs sensitive for this classification were identified. Finally, the efficacy of the prognostic model was validated by cohort (GSE30219, GSE72094 and GSE50081) from GEO database.Conclusions: Our study provided a robust signature for predicting changing prognosis of patients with LUAD. Thus, it appears to be a potentially useful prognostic tool. Moreover, the important relationship between histone acetylation and tumor immune microenvironment was revealed.

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New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication

Qin,

Xie,

Wang

et al. 2024

MedComm

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Cancer is one of the leading causes of death worldwide, and more effective ways of attacking cancer are being sought. Cancer immunotherapy is a new and effective therapeutic method after surgery, radiotherapy, chemotherapy, and targeted therapy. Cancer immunotherapy aims to kill tumor cells by stimulating or rebuilding the body's immune system, with specific efficiency and high safety. However, only few tumor patients respond to immunotherapy and due to the complex and variable characters of cancer immune escape, the behavior and regulatory mechanisms of immune cells need to be deeply explored from more dimensions. Epigenetic modifications, metabolic modulation, and cell‐to‐cell communication are key factors in immune cell adaptation and response to the complex tumor microenvironment. They collectively determine the state and function of immune cells through modulating gene expression, changing in energy and nutrient demands. In addition, immune cells engage in complex communication networks with other immune components, which are mediated by exosomes, cytokines, and chemokines, and are pivotal in shaping the tumor progression and therapeutic response. Understanding the interactions and combined effects of such multidimensions mechanisms in immune cell modulation is important for revealing the mechanisms of immunotherapy failure and developing new therapeutic targets and strategies.

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HBO1 induces histone acetylation and is important for non-small cell lung cancer cell growth

Cited by 21 publications

References 52 publications

A first-in-class HBO1 inhibitor WM-3835 inhibits castration-resistant prostate cancer cell growth in vitro and in vivo

A first-in-class HBO1 inhibitor WM-3835 inhibits castration-resistant prostate cancer cell growth in vitro and in vivo

Histone acetylation modification regulator-mediated tumor microenvironment infiltration characteristics and prognostic model of lung adenocarcinoma patients

New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication

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