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

Pang, Boran; Sui, Shiyao; Wang, Qin; Wu, Junqiang; Yin, Yanling; Xu, Shouping

doi:10.1002/jcp.28364

Cited by 20 publications

(13 citation statements)

References 24 publications

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“…In our study, promoter hypomethylation led to the upregulation of DLEU1 expression in ESCC. In line with our findings, a recent report suggests that decreased DNA methylation and increased histone modifications may contribute to DLEU1 upregulation in cancer [ 46 ]. Drug resistance is the main reason for the failure of chemotherapy.…”

Section: Discussionsupporting

confidence: 93%

DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma

Zhang

Jiang

et al. 2022

J Transl Med

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Background Emerging evidence has highlighted the critical roles of long noncoding RNAs (lncRNAs) in tumor development and progression. However, the biological functions and underlying mechanisms of DLEU1 in esophageal squamous cell carcinoma (ESCC) remain unclear. Methods LncRNA expression in ESCC tissues was explored using lncRNA microarray datasets. The functional roles of DLEU1 in ESCC were demonstrated by a series of in vitro and in vivo experiments. RNA pull-down and immunoprecipitation assays were performed to demonstrate the potential mechanisms of DLEU1. Results In a screen for differentially expressed lncRNAs in ESCC, we determined that DLEU1 was one of the most overexpressed lncRNAs in ESCC tissues and that upregulated DLEU1 expression was associated with a worse prognosis. Functional assays showed that DLEU1 promoted tumor growth by inhibiting cell apoptosis. Mechanistically, DLEU1 could bind and stabilize DYNLL1 by interfering with RNF114-mediated ubiquitination and proteasomal degradation. The DLEU1/DYNLL1 axis subsequently upregulated antiapoptotic BCL2 and promoted cell survival. Furthermore, DLEU1 upregulation was at least partly facilitated by promoter hypomethylation. Notably, targeting DLEU1 sensitized ESCC cells to cisplatin-induced death. Conclusions Our findings suggest that DLEU1-mediated stabilization of DYNLL1 is critical for cell survival and that the DLEU1/DYNLL1 axis may be a promising therapeutic target for ESCC.

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Section: Discussionsupporting

confidence: 93%

DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma

Zhang

Jiang

et al. 2022

J Transl Med

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“…LncRNA DLEU1 predicted a poor prognosis of gastric cancer and promoted cell proliferation through the apparent inhibition of KLF2 ( 18 ). The present study also suggested that the expression of PVT1 and DLEU1 in tumor tissues was notably higher than that in normal tissues ( 18 – 21 ). A positive regulatory relationship existed between lncRNA DLEU1 and lncRNA PVT1, and the effects of lncRNA DLEU1 and lncRNA PVT1 on gastric adenocarcinoma were similar, both of which were highly expressed in tumor tissues.…”

Section: Discussionsupporting

confidence: 70%

The Ferroptosis-Related Noncoding RNA Signature as a Novel Prognostic Biomarker in the Tumor Microenvironment, Immunotherapy, and Drug Screening of Gastric Adenocarcinoma

Chen

Zhu

et al. 2021

Front. Oncol.

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BackgroundFerroptosis is a new type of cell death different from apoptosis, necrosis, autophagy, and pyroptosis. This study aimed to explore the relationship between ferroptosis-related noncoding RNA (ncRNA) and gastric adenocarcinoma with regard to immunity and prognosis.MethodsFerroptosis-related ncRNA expression profiles and clinical pathology and overall survival information were collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database. The ferroptosis-related ncRNA signature was identified by Cox regression analysis and the least absolute shrinkage and selection operator analysis. The survival analysis, receiver operating characteristic (ROC) analysis, and decision curve analysis were adopted to evaluate the prognostic prediction performance of the signature. The correlation between risk and multiple clinical characteristics was analyzed using the chi-square test. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were used for mining functions and pathways. The CIBERSORT, ssGSEA, and ESTIMATE algorithms were used to assess immune infiltration and the tumor microenvironment. The response of immunotherapy was predicted using the Submap algorithm, and the Connectivity Map and the ridge regression model were used to screen and evaluate drugs.ResultsA carcinogenic risk signature was constructed using five ferroptosis-related ncRNAs. It showed an extraordinary ability to predict the prognoses of patients with gastric adenocarcinoma [area under the ROC curve (AUC) after 6 years = 0.689; GSE84426, AUC after 6 years = 0.747]. The lower ferroptosis potential level and lower tumor mutation burden were related to the poor prognoses of patients. The high-risk group had more immune cell recruitment, and the overall effect of the anti-immune checkpoint immunotherapy was not as good as that of the low-risk group. The high- and low-risk groups were enriched in tumor- and immune-related pathways, respectively. The screened antitumor drugs, such as genistein, guanabenz, and betulinic acid, improved the survival of the patients.ConclusionsThe ferroptosis-related ncRNA signature is a potential carcinogenic prognostic biomarker of gastric adenocarcinoma.

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“…COBLL1 is the ancestor of a family of proteins involved in morphogenesis and embryonal patterning in organisms with axial symmetry and is upregulated in castrate-resistant prostate cancer with poor prognosis 37 . Upregulation of DLEU1 can also promote tumorigenesis 38 . A question, therefore, emerges whether excess abdominal fat mediates the development of cancers associated with abdominal obesity 39 , or abdominal obesity and cancer are parallel outcomes with shared genetic predisposition.…”

Section: Discussionmentioning

confidence: 99%

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

Christakoudi

Εvangelou

Riboli

et al. 2021

Sci Rep

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Genetic studies have examined body-shape measures adjusted for body mass index (BMI), while allometric indices are additionally adjusted for height. We performed the first genome-wide association study of A Body Shape Index (ABSI), Hip Index (HI) and the new Waist-to-Hip Index and compared these with traditional indices, using data from the UK Biobank Resource for 219,872 women and 186,825 men with white British ancestry and Bayesian linear mixed-models (BOLT-LMM). One to two thirds of the loci identified for allometric body-shape indices were novel. Most prominent was rs72959041 variant in RSPO3 gene, expressed in visceral adipose tissue and regulating adrenal cell renewal. Highly ranked were genes related to morphogenesis and organogenesis, previously additionally linked to cancer development and progression. Genetic associations were fewer in men compared to women. Prominent region-specific associations showed variants in loci VEGFA and HMGA1 for ABSI and KLF14 for HI in women, and C5orf67 and HOXC4/5 for ABSI and RSPO3, VEGFA and SLC30A10 for HI in men. Although more variants were associated with waist and hip circumference adjusted for BMI compared to ABSI and HI, associations with height had previously been reported for many of the additional variants, illustrating the importance of adjusting correctly for height.

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

Cited by 20 publications

References 24 publications

DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma

DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma

The Ferroptosis-Related Noncoding RNA Signature as a Novel Prognostic Biomarker in the Tumor Microenvironment, Immunotherapy, and Drug Screening of Gastric Adenocarcinoma

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

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