Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

Wang, Junping; Huo, Cheng; Yin, Jinzhu; Liu, Tian; Ma, Lili; Wang, Dongsheng

doi:10.3389/fonc.2021.773644

Cited by 9 publications

(10 citation statements)

References 80 publications

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“…Nevertheless, we must still elaborate on the causal relationship between the methylation of the miR-23 promoter region and the expression of uPA in the future. Wang et al found that DNA methyltransferase 1 can mediate the methylation of the miR-338-5p promoter region, cause the loss of miR-338-5p expression, and ultimately cause a high level of ETS-1 in gliomas ( 63 ). For this reason, in the future, our research group will investigate (1) DNMT-1 expression detection in MM; (2) the effects of DNMT-1 overexpression or knockdown on the expression of miR-23, and on the miR-23 promoter’s methylation; and (3) the recruitment of DNMT-1 to the CpG islands in the promoter region of miR-23.…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Ran¹,

Xu²,

Wang³

et al. 2022

Front. Oncol.

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Multiple myeloma has a long course, with no obvious symptoms in the early stages. However, advanced stages are characterized by injury to the bone system and represent a severe threat to human health. The results of the present work indicate that the hypermethylation of miR-23 promoter mediates the aberrant expression of uPA/PLAU (urokinase plasminogen activator, uPA) in multiple myeloma cells. miR-23, a microRNA that potentially targets uPA’s 3’UTR, was predicted by the online tool miRDB. The endogenous expressions of uPA and miR-23 are related to disease severity in human patients, and the expression of miR-23 is negatively related to uPA expression. The hypermethylation of the promoter region of miR-23 is a promising mechanism to explain the low level of miR-23 or aberrant uPA expression associated with disease severity. Overexpression of miR-23 inhibited the expression of uPA by targeting the 3’UTR of uPA, not only in MM cell lines, but also in patient-derived cell lines. Overexpression of miR-23 also inhibited in vitro and in vivo invasion of MM cells in a nude mouse model. The results therefore extend our knowledge about uPA in MM and may assist in the development of more effective therapeutic strategies for MM treatment.

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Section: Discussionmentioning

confidence: 99%

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Ran¹,

Xu²,

Wang³

et al. 2022

Front. Oncol.

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“…Many studies had shown that DNA methylation was significantly different in normal cells and different subtypes of gliomas, and extensive hypermethylation and hypomethylation of different CpG islands are characteristic of glioma (34). For example, Wang et al demonstrated that hypermethylation of the miR-338-5p promoter regulated the aberrant expression of ETS-1, which was a key regulator of tumor cell proliferation and invasion, and was associated with prognosis of astrocytoma patients (35). There was also a public database-based bioinformatics analysis showing that PODNL1 methylation acted as a prognostic biomarker and correlates with immune infiltration and immune checkpoints in LGG (36).…”

Section: Discussionmentioning

confidence: 99%

Autophagy related DNA methylation signature predict clinical prognosis and immune microenvironment in low-grade glioma

Qiao¹,

Wang²,

Zhang³

et al. 2022

Transl Cancer Res TCR

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Background: Low-grade glioma (LGG) is a common malignant tumor of the central nervous system.The clinical prognosis of different patients varies greatly, so exploring appropriate markers that affect the prognosis and treatment of LGG is important. The purpose of this study was to identify the potential effect of autophagy-related DNA methylation on the prognosis and immune microenvironment in LGG. Methods:The methylation profile, transcription data and corresponding clinical information of 451 patients with LGG were obtained from The Cancer Genome Atlas (TCGA). Another methylation data and clinical information of 110 patients with LGG from Chinese Glioma Genome Atlas (CGGA) were used as the validation set. Through univariate and multivariate COX regression analysis, we identified the autophagy-related genes (ARGs) associated with methylation levels and prognosis, and established a risk assessment signature. The receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival curve were used to verify the model's effectiveness in predicting prognosis. Patients were divided into low-and high-risk groups based on risk scores. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to explore the differences in biological functions between the two groups. ESTIMATE and CIBERSORT algorithms were used to explore differences in immune infiltration and immunotherapy sites. Pearson correlation analysis was used to analyze the relative relationship between methylated cg sites and corresponding genes.Results: A total of 6 ARGs (ARSB, CFLAR, WIPI2, RB1, ERN1, RAB24) were selected that were associated with methylation levels and prognosis. The area under the curve (AUC) =0.96, and the KM survival curve P<0.0001, which proves that the risk assessment model has a good effect in predicting the prognosis ofLGG. GO and KEGG enrichment analysis showed that the model mainly involved major histocompatibility complex (MHC) II receptors, antigen processing and presentation, and immune cell differentiation. In addition, we also found differences in immune infiltration and immune checkpoints between high-and lowrisk groups. Conclusions:The methylation levels of these 6 ARGs have a strong predictive potential for LGG, and the methylation regulation of ARGs has an important impact on the immune microenvironment of LGGs.

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“…[ 42 ] However, another research found that the inhibition of methylated miR-338-5p-5p in the promoter region was related to AOA invision. [ 43 ] It was because of these inconsistent prognostic results that we further used a meta-analysis to research the prognostic value of CIMP in gliomas.…”

Section: Discussionmentioning

confidence: 99%

CIMP-positive glioma is associated with better prognosis: A systematic analysis

Xiao

et al. 2022

Medicine

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Background: CpG island methylator phenotype (CIMP) was closely related to the degree of pathological differentiation of tumors, and it’s an important determinant of glioma pathogenicity. However, the molecular and pathological features of CIMP-positive glioma have not been fully elucidated. In addition, CIMP have been reported to be a useful prognostic marker in several human cancers, yet its prognostic value in gliomas is still controversial. Therefore, we aimed to evaluate gene mutations and pathological features of CIMP-positive glioma and explore the prognostic value of CIMP in gliomas. Methods: We comprehensively searched PubMed, Embase, and MEDLINE for studies describing gene mutations, pathological features and overall survival of gliomas stratified by CIMP status. Odds ratios (OR), hazard ratios (HR), and their 95% confidence intervals (CI) were used to estimate the correlation between CIMP and the outcome parameters. Results: Twelve studies with 2386 gliomas (1051 CIMP-positive and 1335 CIMP-negative) were included. Our results showed that CIMP was more frequent in isocitrate dehydrogenase 1 (IDH1)-mutated gliomas (OR 229.07; 95% CI 138.72–378.26) and 1p19q loss of heterozygosis (LOH) gliomas (OR 5.65; 95% CI 2.66–12.01). Pathological analysis showed that CIMP was common in low-malignant oligodendroglioma (OR 5.51; 95% CI 3.95–7.70) with molecular features including IDH1 mutations and 1p19q LOH, but rare in glioblastoma (OR 0.14; 95% CI 0.10–0.19). However, CIMP showed no obvious correlation with anaplastic oligoastrocytomas (OR 1.57; 95% CI 1.24–2.00) or oligoastrocytomas (OR 0.79; 95% CI 0.35–1.76). Concerning the prognosis, we found that CIMP-positive gliomas had longer overall survival (HR 0.57; 95% CI 0.97–0.16) than CIMP-negative gliomas. Conclusions: CIMP could be used as a potential independent prognostic indicator for glioma.

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Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

Cited by 9 publications

References 80 publications

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Autophagy related DNA methylation signature predict clinical prognosis and immune microenvironment in low-grade glioma

CIMP-positive glioma is associated with better prognosis: A systematic analysis

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