ArticleFrontiers in oncology2021
A Genome-Wide Investigation of Effects of Aberrant DNA Methylation on the Usage of Alternative Promoters in Hepatocellular Carcinoma.
Article in Frontiers in oncology, 2021. 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 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Crosstalk BetweenCancers · 2026Review
- G-quadruplex structures as modulators of alternative promoter usage.NAR genomics and bioinformatics · 2025Article
- Alternative Promoters Drive Transcriptomic Reprogramming and Prognostic Stratification in TNBC.NPJ systems biology and applications · 2025Article
- Transcript PHF19-207 May Be a Long Non-Coding RNA with Tumor-Promoting Role in Colon Cancer.Biomolecules · 2025Article
- New insights into the impact of impaired epigenetic machinery on liver cancer malignant phenotype.Translational cancer research · 2024Article
- Splicing neoantigen discovery with SNAF reveals shared targets for cancer immunotherapy.Science translational medicine · 2024Article
- Dysregulation of transcripts SMAD4-209 and SMAD4-213 and their respective promoters in colon cancer cell lines.Journal of Cancer · 2024Article
- Epigenetic Landscape and Therapeutic Implication of Gene Isoforms of Doublecortin-Like Kinase 1 for Cancer Stem Cells.International journal of molecular sciences · 2023Review
- Review
- Systems Biology Approaches for the Improvement of Oncolytic Virus-Based Immunotherapies.Cancers · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe alternative usage of promoters provides a way to regulate gene expression, has a significant influence on the transcriptome, and contributes to the cellular transformation of cancer. However, the function of alternative promoters (APs) in hepatocellular carcinoma (HCC) has not been systematically studied yet. In addition, the potential mechanism of regulation to the usage of APs remains unclear. DNA methylation, one of the most aberrant epigenetic modifications in cancers, is known to regulate transcriptional activity. Whether DNA methylation regulates the usage of APs needs to be explored. Here, we aim to investigate the effects of DNA methylation on usage of APs in HCC.
methodsPromoter activities were calculated based on RNA-seq data. Functional enrichment analysis was implemented to conduct GO terms. Correlation tests were used to detect the correlation between promoter activity and methylation status. The LASSO regression model was used to generate a diagnostic model. Kaplan-Meier analysis was used to compare the overall survival between high and low methylation groups. RNA-seq and whole-genome bisulfite sequencing (WGBS) in HCC samples were performed to validate the correlation of promoter activity and methylation.
resultsWe identified 855 APs in total, which could be well used to distinguish cancer from normal samples. The correlation of promoter activity and DNA methylation in APs was observed, and the APs with negative correlation were defined as methylation-regulated APs (mrAPs). Six mrAPs were identified to generate a diagnostic model with good performance (AUC = 0.97). Notably, the majority of mrAPs had CpG sites that could be used to predict clinical outcomes by methylation status. Finally, we verified 85.6% of promoter activity variation and 92.3% of methylation changes in our paired RNA-seq and WGBS samples, respectively. The negative correlation between promoter activity and methylation status was further confirmed in our HCC samples.
conclusionThe aberrant methylation status plays a critical role in the precision usage of APs in HCC, which sheds light on the mechanism of cancer development and provides a new insight into cancer screening and treatment.
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