Comprehensive Landscape of HOXA2, HOXA9, and HOXA10 as Potential Biomarkers for Predicting Progression and Prognosis in Prostate Cancer

Song, Yanping; Peng, Xian; Luo, Hong; Dai, Junyong; Bai, Yu; Li, Yuan; Tang, Xianli

doi:10.1155/2022/5740971

Cited by 8 publications

(7 citation statements)

References 30 publications

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“…Even more surprisingly, this function was most enriched for HOXA2 although prostate cancer is more often associated to the deregulated activity of posterior HOX members (see below). However, recent work showed that HOXA2 was associated with aggressive prostate cancer, underlining the robustness of our data (Gao P, et al, 2018; Xia JH, et al, 2018; Song YP., et al, 2022).…”

Section: Resultssupporting

confidence: 83%

A live cell protein complementation assay for ORFeome-wide probing of human HOX interactomes

Jia

Reboulet

Gillet

et al. 2022

Preprint

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Biological pathways rely on the formation of intricate protein interaction networks called interactomes. Getting a comprehensive map of interactomes implies developing tools that allow capturing transient and low affinity protein-protein interactions (PPIs) in live conditions. Here we present an experimental strategy, Cell-PCA (Cell Protein Complementation Assay), which is based on BiFC (Bimolecular Fluorescence Complementation) and high throughput sequencing for ORFeome-wide analyses of different interactomes in the same live cell context. The specificity and sensitivity of Cell-PCA was established by using a wild type and a single amino-acid mutated HOXA9 protein, and the approach was subsequently applied for seven additional human HOX proteins. These proof-of-concept experiments revealed novel molecular properties of HOX interactomes and led to the identification of a novel cofactor of HOXB13 for promoting its proliferative activity in a cancer cell context. Taken together, our work demonstrates that Cell-PCA is pertinent for revealing and, importantly, comparing interactomes between different or highly related bait proteins in the same cell context.

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Section: Resultssupporting

confidence: 83%

A live cell protein complementation assay for ORFeome-wide probing of human HOX interactomes

Jia

Reboulet

Gillet

et al. 2022

Preprint

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“…To understand these dynamics, it is imperative to establish an association between the expression levels of various genes and immune infiltrating molecules. It has been reported that during the progression of prostate cancer (PCa), aberrantly expressed HOXA2, HOXA9, and HOXA10 facilitate the infiltration of dendritic cells, macrophages, and mastocytes [ 80 ]. In EOC, HOXA9 facilitates the transcriptional activation of TGF-β2, which in turn triggers the efflux of chemokines such as CXCL12, IL-6, and VEGF-A in peritoneal fibroblasts [ 73 , 81 ].…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer exploration of oncogenic and clinical impacts revealed that HOXA9 is a diagnostic indicator of tumorigenesis

Shenoy,

Basavarajappa,

Kabekkodu

et al. 2024

Clin Exp Med

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Homeodomain transcription factor A9 (HOXA9) is a member of the HOX cluster family of transcription factors that are crucially involved in embryo implantation, morphogenesis, body axis development, and endothelial cell differentiation. Despite numerous reports on its aberrant expression in a few malignancies, the molecular and functional complexity of HOXA9 across cancers remains obscure. We aimed to analyze the dynamic role of HOXA9 across cancers by identifying, analyzing, and understanding its multiple modes of regulation and functional implications and identifying possible therapeutic avenues. We conducted a comprehensive analysis to determine the role of HOXA9 across cancers. This approach involved the integration of large-scale datasets from public repositories such as the Genomic Data Commons, specifically the Cancer Genome Atlas (GDC-TCGA), across 33 different cancer types. The multiple modes of HOXA9 regulation by genetic and epigenetic factors were determined using online tools, which comprised experimentally validated observations. Furthermore, downstream pathways were identified by predicting the targets of HOXA9 and by performing functional enrichment analysis. We also assessed the clinical significance of HOXA9 in terms of prognosis and stage stratification. This study evaluated the correlation between HOXA9 and tumor-infiltrating molecules and discussed its association with therapeutically approved antineoplastic drugs. HOXA9 was significantly upregulated in 9 tumors and downregulated in 2 cancers. The deregulation of HOXA9 is primarily attributed to epigenetic factors, including promoter DNA methylation and noncoding RNAs (ncRNAs). The HOXA9 transcription factor interacts with PBX/MEIS cofactors and regulates multiple genes involved in cancer-associated EMT, autophagy, the cell cycle, metabolic pathways, Wnt signaling, TGF-β signaling, the AMPK pathway, PI3K/AKT signaling, and NF-κB signaling, thereby establishing control over downstream mechanisms. Differential expression in various clinical stages across cancers was shown to have prognostic significance and to be correlated with tumor-infiltrating immune molecules. The assessment of the correlation of HOXA9 expression with approved antineoplastic drugs revealed that targeting HOXA9 could be the most reliable strategy for preventing cancer progression. HOXA9 is upregulated in the majority of malignancies and drives cancer progression by regulating multiple signaling mechanisms. Hence, HOXA9 could be a reliable diagnostic indicator and a potential therapeutic candidate for solid cancer types.

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“…The low-methylation epigenotype of HOXA2 and HOXA9 in squamous cell carcinoma was associated with idiopathic pulmonary fibrosis and poorer prognosis ( Hata et al, 2020 ). In another study on prostate cancer, HOXA2, HOXA9, and HOXA10 were identified as critical genes, which were both abnormally expressed and associated with clinical outcomes of patients with prostate cancer ( Song et al, 2022 ). In addition to cancers, the CpG methylation of HOXA2 was related to severe fibrosis and the progression in hepatitis B-related chronic liver disease ( Zeybel et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis and experimental validation identified DNA methylation–Related biomarkers and immune-cell infiltration of atherosclerosis

Sun²,

Wei³

et al. 2022

Front. Genet.

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Background: DNA methylation is an important form of epigenetic regulation and is closely related to atherosclerosis (AS). The purpose of this study was to identify DNA methylation–related biomarkers and explore the immune-infiltrate characteristics of AS based on methylation data.Methods: DNA methylation data of 15 atherosclerotic and paired healthy tissues were obtained from Gene Expression Omnibus database. Differential methylation positions (DMPs) and differential methylation regions (DMRs) were screened by the ChAMP R package. The methylation levels of DMPs located on CpG islands of gene promoter regions were averaged. The limma R package was used to screen differentially methylated genes in the CpG islands of the promoter regions. The diagnostic values of the methylation levels were evaluated using the pROC R package. The EpiDISH algorithm was applied to quantify the infiltration levels of seven types of immune cells. Subsequently, three pairs of clinical specimens of coronary atherosclerosis with Stary’s pathological stage III were collected, and the methylation levels were detected by the methylation-specific PCR (MS-PCR) assay. Western blot was performed to detect the protein expression levels of monocyte markers.Results: A total of 110, 695 DMPs, and 918 DMRs were screened in the whole genome. Also, six genes with significant methylation differences in the CpG islands of the promoter regions were identified, including 49 DMPs. In total, three genes (GRIK2, HOXA2, and HOXA3) had delta beta greater than 0.2. The infiltration level of monocytes was significantly upregulated in AS tissues. MS-PCR assay confirmed the methylation status of the aforementioned three genes in AS samples. The Western blot results showed that the expression levels of the monocyte marker CD14 and M1-type macrophage marker CD86 were significantly increased in AS while M2-type macrophage marker protein CD206 was significantly decreased.Conclusion: This study identified potential DNA methylation–related biomarkers and revealed the role of monocytes in early AS.

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Comprehensive Landscape of HOXA2, HOXA9, and HOXA10 as Potential Biomarkers for Predicting Progression and Prognosis in Prostate Cancer

Cited by 8 publications

References 30 publications

A live cell protein complementation assay for ORFeome-wide probing of human HOX interactomes

A live cell protein complementation assay for ORFeome-wide probing of human HOX interactomes

Pan-cancer exploration of oncogenic and clinical impacts revealed that HOXA9 is a diagnostic indicator of tumorigenesis

Bioinformatic analysis and experimental validation identified DNA methylation–Related biomarkers and immune-cell infiltration of atherosclerosis

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