Genome-Wide Identification and Characterization of DNA Methylation and Long Non-Coding RNA Expression in Gastric Cancer

Song, Peng; Wu, Lei; Guan, Wenxian

doi:10.3389/fgene.2020.00091

Cited by 17 publications

(23 citation statements)

References 43 publications

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“…10 -20 % methylation). This was consistent with findings from past literature where biomarkers with a difference in mean methylation of 10 -20 % was considered as "significant" biomarkers with potential for future testing [18], [19], [22], [30].…”

Section: Comparison Of Parametric and Non-parametric Testingsupporting

confidence: 91%

An analytical pipeline for DNA Methylation Array Biomarker Studies

Korbie

Trau

2021

Preprint

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DNA methylation is one of the most commonly studied epigenetic biomarkers, due to its role in disease and development. The Illumina Infinium methylation arrays still remains the most common method to interrogate methylation across the human genome, due to its capabilities of screening over 480, 000 loci simultaneously. As such, initiatives such as The Cancer Genome Atlas (TCGA) have utilized this technology to examine the methylation profile of over 20,000 cancer samples. There is a growing body of methods for pre-processing, normalisation and analysis of array-based DNA methylation data. However, the shape and sampling distribution of probe-wise methylation that could influence the way data should be examined was rarely discussed. Therefore, this article introduces a pipeline that predicts the shape and distribution of normalised methylation patterns prior to selection of the most optimal inferential statistics screen for differential methylation. Additionally, we put forward an alternative pipeline, which employed feature selection, and demonstrate its ability to select for biomarkers with outstanding differences in methylation, which does not require the predetermination of the shape or distribution of the data of interest. Availability: The Distribution test and the feature selection pipelines are available for download at: https://github.com/uqjlu8/DistributionTest Keywords: DNA methylation, Biomarkers, Cancers, Data Distribution, TCGA, 450K

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Section: Comparison Of Parametric and Non-parametric Testingsupporting

confidence: 91%

An analytical pipeline for DNA Methylation Array Biomarker Studies

Korbie

Trau

2021

Preprint

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“…As is known, abnormal DNA methylation is related to many cancers, and this epigenetic disruption may lead to abnormal lncRNA expression in tumor tissues [20]. Evidence has shown that lncRNAs generated in HOX family genes, as HOTAIR, HOTTIP, HOXA11-AS, HOXB-AS4, and HOXC-AS3, were regulated by aberrant DNA methylation in GC [21]. However, the roles and mechanism of lncRNA HOXB-AS4 in GC remain unknown.…”

Section: Introductionmentioning

confidence: 99%

DNA-Methylation-Mediated lncRNA HOXB-AS4 Promotes Gastric Cancer Progression Through Regulating miR-130a-5p/PKP4

Wang¹,

Wang³

et al. 2022

Preprint

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Background：Gastric cancer (GC) is one of the most common cancer in the world, possessing the second leading cause of cancer-related mortality. Long noncoding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis. However, the effect of lncRNA HOXB-AS4 in GC progression and the underlying mechanisms remain unknown. Methods：Firstly, the expression of lncRNA HOXB-AS4 in gastric cancer tissues and cancer cells was investigated according to GEPIA database and Real time fluorescence quantitative PCR(qRT-PCR). Then, MTT, clone formation, Transwell and Western blot were used to study the effects of overexpression or down-regulation of HOXB-AS4 on the proliferation, invasion and epithelial mesenchymal transformation of cancer cells. We further studied the molecular mechanism of HOXB-AS4 by fluorescence in situ hybridization, bioinformatics analysis, luciferase reporting, methylation specific PCR (MSP) and chromatin immunoprecipitation (chip).Results:In the study, the GEPIA database and quantitative Real-Time PCR (qRT-PCR) assay showed that HOXB-AS4 was upregulated in GC tissues and cells. Then, MTT, clone formation, transwell, and western blot assays suggested that overexpression of HOXB-AS4 increased cell proliferation, migration, and invasion, and regulated epithelial-mesenchymal transition (EMT) markers expression, while knockdown of HOXB-AS4 showed the opposite effect. Fluorescence in situ hybridization (FISH) assay found that HOXB-AS4 localized in the cytoplasm of the GSE-1 and AGS cells. Further mechanism experiments, including bioinformatics, luciferase reporter, qRT-PCR, and western blot assays showed that HOXB-AS4 sponged to miR-130a-5p to regulate the PKP4 expression. Knockdown of miR-130a-5p obliterated the effect of HOXB-AS4, which was further abolished by knockdown of PKP4 in vitro and in vivo. Methylation-specific PCR (MSP) and chromatin immunoprecipitation (CHIP) assay showed that overexpression of HOXB-AS4 in GC was mediated by SP1-dependent DNA methylation. Abnormal upregulation of lncRNA HOXB-AS4 contributed to GC progression, which was mediated by DNA methylation. The study clarified that DNA-methylation-mediated HOXB-AS4 played its role through miR-130a-5p/PKP4 axis.Conclusions: Our study provides new insights for the understanding of epigenetic regulation on lncRNA expression in GC, and indicates that HOXB-AS4 could be a biomarker of GC prognosis. Moreover, targeting HOXB-AS4 /miR-130a-5p/PKP4 axis might be a promising strategy to treat GC.

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“…Integrating and reanalyzing the RNA-seq or microarray data using bioinformatics methods may help identify gene regulatory pathways, essential genes, and their associated networks in different diseases, providing information on the possible molecular mechanisms of diseases, potential drug research, and development directions [ 20 , 21 ]. Some studies have precisely revealed details on tumor microenvironment crosstalk [ 22 , 23 ] and the effect of epigenetic modification on tumor development [ 24 ]. In this study, we found that some cytokines, especially CXCL1, showed a significant difference in expression after treatment with belinostat.…”

Section: Introductionmentioning

confidence: 99%

CXCL1 Clone Evolution Induced by the HDAC Inhibitor Belinostat Might Be a Favorable Prognostic Indicator in Triple-Negative Breast Cancer

Han

Zheng

et al. 2021

BioMed Research International

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Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer due to its lack of treatment options. Patients with TNBC frequently develop resistance to chemotherapy. As epigenetic-based antineoplastic drugs, histone deacetylase inhibitors (HDACis) have achieved particular efficacy in lymphoma but are less efficacious in solid tumors, and the resistance mechanism remains poorly understood. In this study, the GSE129944 microarray dataset from the Gene Expression Omnibus database was downloaded, and fold changes at the transcriptome level of a TNBC line (MDA-MB-231) after treatment with belinostat were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to identify the critical biological processes. Construction and analysis of the protein-protein interaction (PPI) network were performed to screen candidate genes related to cancer prognosis. A total of 465 DEGs were identified, including 240 downregulated and 225 upregulated genes. The cytokine-cytokine receptor pathway was identified as being significantly changed. Furthermore, the expression of CXCL1 was implicated as a favorable factor in the overall survival of breast cancer patients. With in vitro approaches, we also showed that belinostat could induce the expression of CXCL1 in another 2 TNBC cell lines (BT-549 and HCC-1937). We speculate that belinostat-induced CXCL1 expression could be one of the results of the stress clone evolution of cells after HDACi treatment. These findings provide new insights into clone evolution during HDACi treatment, which might guide us to a novel perspective that various mutation-targeted treatments should be implemented during the whole treatment cycle.

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Genome-Wide Identification and Characterization of DNA Methylation and Long Non-Coding RNA Expression in Gastric Cancer

Cited by 17 publications

References 43 publications

An analytical pipeline for DNA Methylation Array Biomarker Studies

An analytical pipeline for DNA Methylation Array Biomarker Studies

DNA-Methylation-Mediated lncRNA HOXB-AS4 Promotes Gastric Cancer Progression Through Regulating miR-130a-5p/PKP4

CXCL1 Clone Evolution Induced by the HDAC Inhibitor Belinostat Might Be a Favorable Prognostic Indicator in Triple-Negative Breast Cancer

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