Upregulation of DLEU1 expression by epigenetic modification promotes tumorigenesis in human cancer

The function of DLEU1 in human cancer is largely unknown. The Cancer Genome Atlas data were applied to identify the landscape of differential genes between tumor tissues and normal tissues, which was further validated by our cohort data and pan‐cancer data including 33 cancer types with 11,060 patie...

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Bibliographic Details
Published in:Journal of cellular physiology 2019-10, Vol.234 (10), p.17420-17432
Main Authors: Pang, Boran, Sui, Shiyao, Wang, Qin, Wu, Junqiang, Yin, Yanling, Xu, Shouping
Format: Article
Language:English
Subjects:
Cancer
Carcinogenesis - genetics
Carcinogenesis - metabolism
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation - genetics
Cell Transformation, Neoplastic - genetics
Deoxyribonucleic acid
DLEU1
DNA
DNA methylation
Epigenesis, Genetic - genetics
epigenetic modification
Epigenetics
Gene expression
Gene Expression Regulation, Neoplastic - genetics
Genomes
Humans
lncRNAs
Loci
prognosis
RNA, Long Noncoding - genetics
Tumor Suppressor Proteins - metabolism
Tumorigenesis
Up-Regulation
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Summary:The function of DLEU1 in human cancer is largely unknown. The Cancer Genome Atlas data were applied to identify the landscape of differential genes between tumor tissues and normal tissues, which was further validated by our cohort data and pan‐cancer data including 33 cancer types with 11,060 patients. Next, DLEU1 was selected to validate the novel finding and result showed that it promoted tumorigenesis in vitro and in vivo. Mechanistically, DLEU1 promotes SRP4 expression via increasing H3K27ac enrichment to SRP4 locus epigenetically. Moreover, epigenetic modification leads to upregulation of DLEU1 expression via decreased DNA methylation and increased H3K27ac and H3K4me3 histone modification in its locus. Finally, high expression of DLEU1 correlates with worse prognosis not only in specific cancer type patients but also in patients in the pan‐cancer cohort. In summary, the work broadens the function landscape of known long noncoding RNAs in human cancer and provides novel insights into their roles in tumorigenesis. DLEU1 promotes SRP4 expression via increasing H3K27ac enrichment to SRP4 locus epigenetically. Moreover, epigenetic modification leads to upregulation of DLEU1 expression via decreased DNA methylation and increased H3K27ac and H3K4me3 histone modification in its locus.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.28364