Biological implications and therapeutic significance of DNA methylation regulated genes in cervical cancer

Bhat, Sevitha; Kabekkodu, Shama Prasada; Noronha, Ashish; Satyamoorthy, Kapaettu

doi:10.1016/j.biochi.2015.12.018

Cited by 50 publications

(38 citation statements)

References 201 publications

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“…40 During carcinogenesis, both global loss of DNA methylation and gene-specific hypermethylation of anticancer genes have been reported in different types of cancer, including cervical cancer. 2,[37][38][39] Global loss of DNA methylation is primarily seen in repetitive elements, comprising approximately half of the human genome. Besides, progressive loss of DNA methylation may lead to activation of proto-oncogenes and transposable elements resulting in genomic instability and thus contributing to carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…10 The diagnostic and prognostic significance of methylated genes in cervical cancer have been extensively reviewed. 2,14,15 A majority of the cervical cancer DNA methylation studies have validated genes which are also reported in other cancers, and only a few of these markers are specific for cervical cancer with high sensitivity and specificity. 16 In addition, studies have implicated ethnicity as one of the confounding factors for the development of DNA methylation-based biomarkers.…”

Section: Introductionmentioning

confidence: 99%

“…Epigenetic mechanisms leading to global hypomethylation and gene-specific hypermethylation play a key role in carcinogenesis, including cervical cancer. 2,3 Removal of methyl group from the cytosine residue of the DNA resulting in global hypomethylation is mediated by several non-enzymatic mechanisms or by the action of ten-eleven translocation (TET) family of alphaglutarate-dependent oxygenases. 4 Oxidative by-products of 5-hydroxymethylcytosine (5-hmC), such as 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), are part of cytosine deaminase pathway and participate in DNA repair process.…”

Section: Introductionmentioning

confidence: 99%

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Aberrant gene-specific DNA methylation signature analysis in cervical cancer

et al. 2017

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Multicomponent molecular modifications such as DNA methylation may offer sensitive and specific cervical intraepithelial neoplasia and cervical cancer biomarkers. In this study, we tested cervical tissues at various stages of tumor progression for 5-methylcytosine and 5-hydroxymethylcytosine levels and also DNA promoter methylation profile of a panel of genes for its diagnostic potential. In total, 5-methylcytosine, 5-hydroxymethylcytosine, and promoter methylation of 33 genes were evaluated by reversed-phase high-performance liquid chromatography, enzyme-linked immunosorbent assay based technique, and bisulfate-based next generation sequencing. The 5-methylcytosine and 5-hydroxymethylcytosine contents were significantly reduced in squamous cell carcinoma and receiver operating characteristic curve analysis showed a significant difference in (1) 5-methylcytosine between normal and squamous cell carcinoma tissues (area under the curve = 0.946) and (2) 5-hydroxymethylcytosine levels among normal, squamous intraepithelial lesions and squamous cell carcinoma. Analyses of our next generation sequencing results and data from five independent published studies consisting of 191 normal, 10 low-grade squamous intraepithelial lesions, 21 high-grade squamous intraepithelial lesions, and 335 malignant tissues identified a panel of nine genes (ARHGAP6, DAPK1, HAND2, NKX2-2, NNAT, PCDH10, PROX1, PITX2, and RAB6C) which could effectively discriminate among the various groups with sensitivity and specificity of 80%-100% (p < 0.05). Furthermore, 12 gene promoters (ARHGAP6, HAND2, LHX9, HEY2, NKX2-2, PCDH10, PITX2, PROX1, TBX3, IKBKG, RAB6C, and DAPK1) were also methylated in one or more of the cervical cancer cell lines tested. The global and gene-specific methylation of the panel of genes identified in our study may serve as useful biomarkers for the early detection and clinical management of cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aberrant gene-specific DNA methylation signature analysis in cervical cancer

et al. 2017

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“…In both cervical and endometrial cancer, specific genes involved in various pathways are known to be methylated. In cervical cancer, these genes include tumor protein p73, fragile histidine triad (FHIT), death-associated protein kinase 1 and PRDI-BF and RIZ domain containing 14 in the apoptotic pathway; cyclin A1 (CCNA1) and double C2-like domain β in the cell cycle; adenomatous polyposis coli (APC) and secreted frizzled-related protein (SFRP) in the Wnt/β-catenin pathway; Fanconi anemia, complementation group F, O-6-methylguanine-DNA methyltransferase, human MutL homolog 1 (hMLH1) and CCNA1 in DNA repair; FHIT, retinoic acid receptor-β and myelin and lymphocyte in the cell growth pathway; and CXC chemokine receptor 4 and cell adhesion molecule 1, which are involved in cell adhesion (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). In endometrial cancer, the following genes are methylated: APC, caspase-8, checkpoint with forkhead-associated and ring finger, E-cadherin, hMLH1, p73, progesterone receptor, phosphatase and tensin homologue deleted on chromosome 10, Ras association domain family 1 isoform A and thrombospondin 2 .…”

Section: Introductionmentioning

confidence: 99%

Recent findings on epigenetic gene abnormalities involved in uterine cancer

Yanokura

Banno

Kobayashi

et al. 2017

Molecular and Clinical Oncology

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Abstract. Selective aberrant genetic effects that do not depend on abnormal DNA sequences are referred to as epigenetic abnormalities and are involved in carcinogenesis. In uterine cancer, various genes involved in apoptosis, cell cycle, DNA repair, cell proliferation and cell adhesion are abnormally methylated, resulting in gene silencing. Reversal of such epigenetic abnormalities in cancer cells is a potential strategy for cancer therapy, and studies on epigenetic abnormalities and treatment methods in uterine cancer are in progress. These include the evaluation of 5-hydroxymethylcytosine, which is present in cancer tissues at lower levels compared with those in normal tissues, as a prognostic marker in cervical cancer; combination therapy with 5-azacytidine and cisplatin; combination treatment focusing on tumor necrosis factor-related apoptosis-inducing ligand in cervical cancer; studies focusing on DNA mismatch repair in endometrial cancer; and use of a demethylating agent to reactivate tumor suppressor genes and inhibit tumor proliferation. Detection of epigenetic changes using biomarkers may be used for histological classification, evaluation of disease progression and identification of compounds that are able to modulate epigenetic changes and may be useful for uterine cancer treatment.

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“…37 Recent epidemiological and molecular studies have shown that CC frequently involves HPV infection and genetic and/or epigenetic changes, both being essential for initiation, development, and progression of this disease. 38 More recently, folate deficiency was proposed to affect chromosomal stability at the FRA3B site, located in the FHIT gene. This instability could collaborate with the evolution of CIN to invasive cancer.…”

Section: Fhit and Breast Cancermentioning

confidence: 99%