Integrative bioinformatics and experimental analysis revealed down-regulated CDC42EP3 as a novel prognostic target for ovarian cancer and its roles in immune infiltration

Yan, Yuanliang; Liang, Qiuju; Xu, Zhijie; Yi, Qiaoli

doi:10.7717/peerj.12171

Cited by 8 publications

(10 citation statements)

References 43 publications

(50 reference statements)

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“…Previous studies have indicated that the bio functional roles of CDC42EP3 in regulating cell shape change, actomyosin contractility and pathological fibroblast activation ( Farrugia and Calvo, 2016 ). Additionally, CDC42EP3 is also associated with the occurrence and progression of human cancers, such as colorectal cancer ( Feng et al, 2021 ), ovarian cancer ( Yan et al, 2021 ), and glioma ( Yang et al, 2022 ). HIST1H4L, known as H4 Clustered Histone 13 (H4C13), is essential nuclear proteins responsible for the nucleosome structure of the chromosomal fiber in eukaryotes.…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis of DNA methylation and gene expression data for the diagnosis and underlying mechanism of Parkinson’s disease

Ding

Liang²,

Guo³

et al. 2022

Front. Aging Neurosci.

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BackgroundParkinson’s disease (PD) is the second most common progressive neurodegenerative disorder and the leading cause of disability in the daily activities. In the management of PD, accurate and specific biomarkers in blood for the early diagnosis of PD are urgently needed. DNA methylation is one of the main epigenetic mechanisms and associated with the gene expression and disease initiation of PD. We aimed to construct a methylation signature for the diagnosis of PD patients, and explore the potential value of DNA methylation in therapeutic options.Materials and methodsWhole blood DNA methylation and gene expression data of PD patients as well as healthy controls were extracted from Gene Expression Omnibus database. Next, differentially expressed genes (DEGs) and differentially methylated genes (DMGs) between PD patients and healthy controls were identified. Least absolute shrinkage and selection operator cox regression analysis was carried out to construct a diagnostic signature based on the overlapped genes. And, the receiver operating characteristic (ROC) curves were drawn and the area under the curve (AUC) was used to assess the diagnostic performance of the signature in both the training and testing datasets. Finally, gene ontology and gene set enrichment analysis were subsequently carried out to explore the underlying mechanisms.ResultsWe obtained a total of 9,596 DMGs, 1,058 DEGs, and 237 overlapped genes in the whole blood between PD patients and healthy controls. Eight methylation-driven genes (HIST1H4L, CDC42EP3, KIT, GNLY, SLC22A1, GCM1, INO80B, and ARHGAP26) were identified to construct the gene expression signature. The AUCs in predicting PD patients were 0.84 and 0.76 in training dataset and testing dataset, respectively. Additionally, eight methylation-altered CpGs were also identified to construct the CpGs signature which showed a similarly robust diagnostic capability, with AUCs of 0.8 and 0.73 in training dataset and testing dataset, respectively.ConclusionWe conducted an integrated analysis of the gene expression and DNA methylation data, and constructed a methylation-driven genes signature and a methylation-altered CpGs signature to distinguish the patients with PD from healthy controls. Both of them had a robust prediction power and provide a new insight into personalized diagnostic and therapeutic strategies for PD.

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Section: Discussionmentioning

confidence: 99%

Integrative analysis of DNA methylation and gene expression data for the diagnosis and underlying mechanism of Parkinson’s disease

Ding

Liang²,

Guo³

et al. 2022

Front. Aging Neurosci.

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“…M6A methylation mechanism have greatly contributed to the field of epigenetics. Methyltransferases, demethylases, and reading proteins jointly regulate m6A levels in downstream genes, thereby promoting tumor initiation and progression ( Xu et al, 2020b ; Yan et al, 2021 ). M6A RNA methylation comprises the m6A methyltransferase, m6A demethylase, and m6A binding proteins which regulate mRNA precursor shear, mRNA stability, and translation.…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

Liu

2022

Front. Genet.

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N6-methyladenosine (m6A) is a dynamic, reversible post-transcriptional modification, and the most common internal modification of eukaryotic messenger RNA (mRNA). Considerable evidence now shows that m6A alters gene expression, thereby regulating cell self-renewal, differentiation, invasion, and apoptotic processes. M6A methylation disorders are directly related to abnormal RNA metabolism, which may lead to tumor formation. M6A methyltransferase is the dominant catalyst during m6A modification; it removes m6A demethylase, promotes recognition by m6A binding proteins, and regulates mRNA metabolic processes. Bladder cancer (BC) is a urinary system malignant tumor, with complex etiology and high incidence rates. A well-differentiated or moderately differentiated pathological type at initial diagnosis accounts for most patients with BC. For differentiated superficial bladder urothelial carcinoma, the prognosis is normally good after surgery. However, due to poor epithelial cell differentiation, BC urothelial cell proliferation and infiltration may lead to invasive or metastatic BC, which lowers the 5-years survival rate and significantly affects clinical treatments in elderly patients. Here, we review the latest progress in m6A RNA methylation research and investigate its regulation on BC occurrence and development.

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“…Yan et al also reported cell division cycle 42 effector protein 3 (CDC42EP3) as a possible target gene of m 6 A, which was downregulated by m 6 A regulators in the OC cells and tissues [ 80 ]. Interestingly, the expression of CDC42EP3 was reported to be correlated with the various TICs, including natural killer cells, T central memory cells, and T gamma delta cells [ 80 ]. Jiang et al further elucidated the mechanism of m 6 A regulatory factors involved in immune responses [ 54 ].…”

Section: A and Ocmentioning

confidence: 99%

Roles of N6-methyladenosine (m6A) modifications in gynecologic cancers: mechanisms and therapeutic targeting

et al. 2022

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Uterine and ovarian cancers are the most common gynecologic cancers. N6−methyladenosine (m6A), an important internal RNA modification in higher eukaryotes, has recently become a hot topic in epigenetic studies. Numerous studies have revealed that the m6A-related regulatory factors regulate the occurrence and metastasis of tumors and drug resistance through various mechanisms. The m6A-related regulatory factors can also be used as therapeutic targets and biomarkers for the early diagnosis of cancers, including gynecologic cancers. This review discusses the role of m6A in gynecologic cancers and summarizes the recent advancements in m6A modification in gynecologic cancers to improve the understanding of the occurrence, diagnosis, treatment, and prognosis of gynecologic cancers.

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Integrative bioinformatics and experimental analysis revealed down-regulated CDC42EP3 as a novel prognostic target for ovarian cancer and its roles in immune infiltration

Cited by 8 publications

References 43 publications

Integrative analysis of DNA methylation and gene expression data for the diagnosis and underlying mechanism of Parkinson’s disease

Integrative analysis of DNA methylation and gene expression data for the diagnosis and underlying mechanism of Parkinson’s disease

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

Roles of N6-methyladenosine (m6A) modifications in gynecologic cancers: mechanisms and therapeutic targeting

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