ArticleCell communication and signaling : CCS2022
Epigenetic silencing and tumor suppressor gene of HAND2 by targeting ERK signaling in colorectal cancer.
Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Pooled it
- Promoter Hypermethylation-Induced Silencing of FXYD1 Drives Breast Cancer Metastasis via DDX5-Mediated Wnt/β-Catenin Pathway Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DNA methylation driven genes shape prognosis and tumor immune landscape in rectal cancer.Discover oncology · 2026Article
- Urinary DNA methylation biomarkers for bladder cancer diagnosis: a single center case-control study.Frontiers in oncology · 2026Article
- Non-invasive colorectal cancer biomarkers: HAND2 and GPM6A methylation in circulating tumour DNA.Cancer cell international · 2025Article
- Pan-cancer and multiomics: advanced strategies for diagnosis, prognosis, and therapy in the complex genetic and molecular universe of cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Mechanisms of GPM6A in Malignant Tumors.Cancer reports (Hoboken, N.J.) · 2025Review
- Predictive nomogram of the clinical outcomes of colorectal cancer based on methylated SEPT9 and intratumoral IL-10Journal of translational medicine · 2024Article
- Distinct HAND2/HAND2-AS1 Expression Levels May Fine-Tune Mesenchymal and Epithelial Cell Plasticity of Human Mesenchymal Stem Cells.International journal of molecular sciences · 2023Article
- Consequences of aberrated DNA methylation in Colon Adenocarcinoma: a bioinformatic-based multi-approach.BMC genomic data · 2022Article
- Correction: Epigenetic silencing and tumor suppressor gene of HAND2 by targeting ERK signaling in colorectal cancer.Cell communication and signaling : CCS · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe screening biomarkers for early detection of colorectal cancer (CRC) is lacking. The aim is to identify epigenetic silenced genes and clarify its roles and underlying mechanism in CRC. We conducted integrative analyses of epigenome-wide Human Methylation 450 K arrays and transcriptome to screen out candidate epigenetic driver genes with transcription silencing. Methylated silencing HAND2 were identified and verified in large CRC cohort. The mechanism of HAND2 expression by promoter inhibition were clarified both in vitro and vivo assays. Cell biofunctional roles of HAND2 methylation was investigated in CRC cells. HAND2 reconstitution were constructed by lentivirus plasmid and tumor xenograft model of HAND2 were built subcutaneously. Genomic mRNA analysis by RNA-sequencing and subsequent GSEA analysis were performed to identify potential target of HAND2 and qPCR/WB was conducted to identify the results.
resultsWe firstly reported high frequency of HAND2 methylation in promoter in CRC and hypermethylation was negatively correlated with expression silencing and leaded to poor survival in several CRC cohort patients. 5-Aza treatment to demethylated HAND2 could revert its expression in CRC cells. Functionally, HAND2 reconstitution can inhibit cell proliferation, invasion and migration in vitro. In tumor xenograft, HAND2 reconstruction significantly repressed tumor growth when compared to control vector. Thousands of aberrant expressed genes were observed in the heatmap of RNA-sequencing data. HAND2 reconstitution could bind to ERK and reduce its phosphorylation by CoIP assay. These above results showed HAND2 reconstitution perturbed the activation of MAPK/ERK signaling by reduction of ERK phosphorylation.
conclusionsHAND2 is one tumor suppressor by targeting ERK signaling and one potential epigenetic driver gene in CRC. Video Abstract.
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