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Identification and validation of methylated differentially expressed miRNAs and immune infiltrate profile in EBV-associated gastric cancer.


ABSTRACT:

Background

The recent discovery of cancer/tissue specificity of miRNA has indicated its great potential as a therapeutic target. In Epstein-Barr virus-associated gastric cancer (EBVaGC), host genes are affected by extensive DNA methylation, including miRNAs. However, the role of methylated miRNA in the development of EBVaGC and immune cell infiltration has largely remained elusive.

Results

After crossmatching the DNA methylation and expression profile of miRNA and mRNA in the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas Research Network (TCGA), we discovered that miR-129-2-3p was significantly suppressed due to hypermethylation on its enhancer in EBVaGC. The differentially expressed genes (DEGs) added up to 30, among which AKAP12 and LARP6 were predicted to be the target genes of miR-129-2-3p and negatively correlated with patients' survival. Accordingly, miR-129-2-3p was significantly down-regulated in tumor samples in 26 (65%) out of 40 cases in our cohort (P?+ T cell, macrophage and dendritic cell infiltrates were significantly enriched for the prognostic-indicated hub genes.

Conclusion

This study has provided a comprehensive analysis of differentially expressed miRNAs and mRNAs associated with genome-wide DNA methylation by integrating multi-source data including transcriptome, methylome and clinical data from GEO and TCGA, QPCR of tumor samples and cell function assays. It also gives a hint on the relationships between methylated miRNA, DEGs and the immune infiltration. Further experimental and clinical investigations are warranted to explore the underlying mechanism and validate our findings.

SUBMITTER: Zhu M 

PROVIDER: S-EPMC7845045 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Identification and validation of methylated differentially expressed miRNAs and immune infiltrate profile in EBV-associated gastric cancer.

Zhu Mansheng M   Liang Qixiang Q   Chen Tao T   Kong Qian Q   Ye Gengtai G   Yu Shitong S   Li Xunjun X   He Qinglie Q   Liu Hao H   Hu Yanfeng Y   Yu Jiang J   Li Guoxin G  

Clinical epigenetics 20210129 1


<h4>Background</h4>The recent discovery of cancer/tissue specificity of miRNA has indicated its great potential as a therapeutic target. In Epstein-Barr virus-associated gastric cancer (EBVaGC), host genes are affected by extensive DNA methylation, including miRNAs. However, the role of methylated miRNA in the development of EBVaGC and immune cell infiltration has largely remained elusive.<h4>Results</h4>After crossmatching the DNA methylation and expression profile of miRNA and mRNA in the Gene  ...[more]

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