Epigenetics in oral squamous cell carcinoma

Hema, K.; Smitha, T; Sheethal, H S; Mirnalini, S Angeline

doi:10.4103/jomfp.jomfp_150_17

Cited by 78 publications

(80 citation statements)

References 56 publications

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“…Therefore, it is urgent to identify reliable prognostic biomarkers for treatment failure, as well as to develop innovative drug targets for more effective and less toxic treatment. Recent evidence indicates that epigenetic alterations, apart from genetic alteration, have been linked with the pathogenesis and clinical outcome in OSCC carcinogenesis [3,4]. The most common epigenetic alteration in OSCC is aberrant DNA methylation, which can silence gene expression and regulate biological processes, and play an important role in cancer initiation, progression, and metastasis [5,6].…”

Section: Introductionmentioning

confidence: 99%

MiR-30a and miR-379 modulate retinoic acid pathway by targeting DNA methyltransferase 3B in oral cancer

et al. 2020

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Background: Epigenetic silencing of retinoic acid (RA) signaling-related genes have been linked with the pathogenesis and clinical outcome in oral squamous cell carcinoma (OSCC) carcinogenesis. However, the precise mechanisms underlying the abnormal silencing of RA signaling-related genes in OSCC have not been well investigated. Methods: Using combined analysis of genome-wide gene expression and methylation profile from 40 matched normaltumor pairs of OSCC specimens, we found a set of retinoid signaling related genes are frequently hypermethylated and downregulated in OSCC patient samples, including alcohol dehydrogenase, iron containing 1 (ADHFE1) and aldehyde dehydrogenase 1 family, member A2 (ALDH1A2), which are the important rate-limiting enzymes in synthesis of RA. The expression of ADHFE1 and ALDH1A2 in OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. The binding sites of miR-30a and miR-379 with DNA methyltransferase 3B (DNMT3B) were predicted using a series of bioinformatic tools, and validated using dual luciferase assay and Western blot analyses. The functions of miR-30a, miR-379, and DNMT3B were accessed by growth and colony formation analyses using gain-and loss-of-function approaches. Chromatin immunoprecipitation (ChIP) was performed to explore the molecular mechanisms by arecoline and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) treatment. Results: We demonstrated that deregulated miR-30a and miR-379 could represent a mechanism for the silencing of ADHFE1 and ALDH1A2 in OSCC through targeting DNMT3B. Ectopic expression of miR-30a and miR-379 could induce re-expression of methylation-silenced ADHFE1 and ALDH1A2, and lead to growth inhibition in oral cancer cells. Furthermore, the dysregulation of the miRNAs and DNMT-3B may result from exposure to tobacco smoking and betel quid chewing.

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Section: Introductionmentioning

confidence: 99%

MiR-30a and miR-379 modulate retinoic acid pathway by targeting DNA methyltransferase 3B in oral cancer

et al. 2020

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“…It is performed by a series of enzymes known as DNA methyltransferases (DNMTs). These enzymes catalyze the covalent addition of a methyl group to the carbon-5 position of cytosine bases that are located 5' to a guanosine base in a CpG dinucleotide (52).…”

Section: Epigeneticsmentioning

confidence: 99%

“…Conversely, hypo/demethylation of the promoter of proto-oncogenes may lead to increased expression of these genes (50). An imbalance in tumor suppressor gene methylation status has often been reported following exposure to tobacco-derived carcinogens and other environmental compounds including cadmium, arsenic and nickel (52).…”

Section: Epigeneticsmentioning

confidence: 99%

Epigenetics of oral and oropharyngeal cancers (Review)

et al. 2018

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Oral and oropharyngeal cancers represent the two most common malignancies of the head and neck region. The major risk factors for these cancers include alcohol consumption, tobacco use (via smoking or chewing) and high-risk human papillomavirus infection. The transition from normal epithelium to premalignant tissue and finally carcinoma is in part caused by a summation of genetic and epigenetic modifications. Epigenetic refers to modifications in the way the genome is expressed in cells. The most common examples of epigenetic control of gene expression are DNA methylation, histone modification and regulation by small non-coding RNAs. The aim of the current paper was to review the recent studies on the main epigenetic changes that have been suggested to serve a role in the carcinogenesis process and progression of oral and oropharyngeal cancers. Furthermore, it is discussed how the epigenetic changes may be used as potential predictive biomarkers and how recent findings in the field may impact the personalized cancer therapy approach for these tumors.

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“…Invasion and metastasis are fundamental characteristics of advanced TSCC, and are the principal reasons behind the unfavorable outcomes for patients with TSCC. Numerous studies have suggested that Wnt signaling is associated with the metastasis and progression of TSCC (26)(27)(28)(29)(30); however, to the best of our knowledge, the specific ligand partners associated with Wnt signaling in this disease have not been identified. The present study revealed that Wnt7a was upregulated in TSCC tissues compared with in the corresponding adjacent non-cancerous tissues from two patient cohorts.…”

Section: Discussionmentioning

confidence: 99%

Wnt7a predicts poor prognosis, and contributes to growth and metastasis in tongue squamous cell carcinoma

et al. 2019

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Regional and distant metastases are the principal reasons underlying the high mortality rate associated with tongue squamous cell carcinoma (TSCC); however, the precise molecular mechanisms involved in tongue tumorigenesis remain unknown. The present study aimed to determine the expression and mechanism of regulation of Wnt7a in the growth and metastasis of TSCC. Wnt7a mRNA and protein expression levels were examined in TSCC tissues using reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining. A loss-of-function assay was performed in TSCC cell lines using Wnt7a small interfering RNA or short hairpin RNA, after which, cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8, tumorigenicity and Transwell assays, respectively. Epithelial-mesenchymal transition (EMT)-associated proteins were detected by western blotting. The mRNA and protein expression levels of Wnt7a were significantly upregulated in cancer tissues compared with in the adjacent non-cancerous tissues. Clinical analysis indicated that Wnt7a expression was associated with T classification, lymph node metastasis and pathological differentiation, and high Wnt7a expression predicted a short recurrence-free survival for patients with TSCC. Silencing Wnt7a expression suppressed cell proliferation, migration and invasion, and reversed the EMT phenotype in TSCC cell lines. The present study revealed that Wnt7a may be upregulated in TSCC, where it may participate in modulating cell proliferation, migration, invasion and the EMT of TSCC. Therefore, Wnt7a should be considered a novel oncogene, and a potential prognostic and therapeutic target for patients with TSCC.

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Epigenetics in oral squamous cell carcinoma

Cited by 78 publications

References 56 publications

MiR-30a and miR-379 modulate retinoic acid pathway by targeting DNA methyltransferase 3B in oral cancer

MiR-30a and miR-379 modulate retinoic acid pathway by targeting DNA methyltransferase 3B in oral cancer

Epigenetics of oral and oropharyngeal cancers (Review)

Wnt7a predicts poor prognosis, and contributes to growth and metastasis in tongue squamous cell carcinoma

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