{"title":"HDAC1: a promising target for cancer treatment: insights from a thorough analysis of tumor functions.","authors":"Jiaojiao Xie, Rui Liu, Ying Cai, Dina Liu","doi":"10.21037/tcr-24-23","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Many significant findings from recent studies have revealed the significance of histone deacetylase 1 (HDAC1) in the development of tumors and its strong association with tumor prognosis; these studies have mainly focused on one single cancer such as in lung cancer, breast cancer, and hepatocellular carcinoma (HCC). To date, there has been no comprehensive analysis and pan-analysis conducted from the overall perspective of cancer across all types. Hence, we analyzed public databases, conducted tube formation assay, and immunohistochemistry (IHC) staining of HDAC1 on six kinds of clinical samples to explore the prognostic and oncogenic effects of HDAC1 on 33 tumors for the first time. There currently remains a lack of efficient testing methods, therapies, and diagnostic and prognostic markers of tumor formation and development in different tumors.</p><p><strong>Methods: </strong>Our initial objective was to investigate the possible cancer-causing functions of HDAC1 in 33 different types of tumors by utilizing The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and many different online websites, such as Tumor IMmune Estimation Resource 2 (TIMER2), Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Genotype Tissue Expression (GTEx) database, Clinical Proteomic Tumor Analysis Consortium (CPTAC) dataset, and University of ALabama at Brimingham CANcer data analysis portal (UALCAN) tool, and so on. We even used small interfering RNA (siRNA) to knock down HDAC2 in HCC cell lines. IHC of HDAC1 was performed.</p><p><strong>Results: </strong>HDAC1 exhibited high expression in numerous tumors, and strong correlations were observed between the messenger RNA (mRNA) levels of HDAC1 and the prognosis of individuals diagnosed with tumors. Human umbilical vein endothelial cells (HUVECs) tube formation and migration were significantly inhibited by conditioned media from HCC cells treated with siRNA of HDAC1. Several types of cancer have been found to exhibit elevated levels of phosphorylation at S421. Furthermore, as in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), and kidney renal papillary cell carcinoma (KIRP), HDAC1 expression was found to be correlated with inflammatory cell infiltration.</p><p><strong>Conclusions: </strong>The levels of HDAC1 are expected to adapt to clinical adjuvant targeted therapy in most types of solid cancer.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5300-5315"},"PeriodicalIF":1.5000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543092/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-24-23","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/23 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Many significant findings from recent studies have revealed the significance of histone deacetylase 1 (HDAC1) in the development of tumors and its strong association with tumor prognosis; these studies have mainly focused on one single cancer such as in lung cancer, breast cancer, and hepatocellular carcinoma (HCC). To date, there has been no comprehensive analysis and pan-analysis conducted from the overall perspective of cancer across all types. Hence, we analyzed public databases, conducted tube formation assay, and immunohistochemistry (IHC) staining of HDAC1 on six kinds of clinical samples to explore the prognostic and oncogenic effects of HDAC1 on 33 tumors for the first time. There currently remains a lack of efficient testing methods, therapies, and diagnostic and prognostic markers of tumor formation and development in different tumors.
Methods: Our initial objective was to investigate the possible cancer-causing functions of HDAC1 in 33 different types of tumors by utilizing The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and many different online websites, such as Tumor IMmune Estimation Resource 2 (TIMER2), Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Genotype Tissue Expression (GTEx) database, Clinical Proteomic Tumor Analysis Consortium (CPTAC) dataset, and University of ALabama at Brimingham CANcer data analysis portal (UALCAN) tool, and so on. We even used small interfering RNA (siRNA) to knock down HDAC2 in HCC cell lines. IHC of HDAC1 was performed.
Results: HDAC1 exhibited high expression in numerous tumors, and strong correlations were observed between the messenger RNA (mRNA) levels of HDAC1 and the prognosis of individuals diagnosed with tumors. Human umbilical vein endothelial cells (HUVECs) tube formation and migration were significantly inhibited by conditioned media from HCC cells treated with siRNA of HDAC1. Several types of cancer have been found to exhibit elevated levels of phosphorylation at S421. Furthermore, as in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), and kidney renal papillary cell carcinoma (KIRP), HDAC1 expression was found to be correlated with inflammatory cell infiltration.
Conclusions: The levels of HDAC1 are expected to adapt to clinical adjuvant targeted therapy in most types of solid cancer.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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