DNA methylation methods: Global DNA methylation and methylomic analyses

Li, Shizhao; Tollefsbol, Trygve O.

doi:10.1016/j.ymeth.2020.10.002

Cited by 122 publications

(76 citation statements)

References 288 publications

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“…DNA methylation, one of the most important epigenetic alterations, plays a crucial role in carcinogenesis (18)(19)(20). Accumulating pieces of evidence have shown that frequent hypermethylation of a target gene leads to its reduced expression level, therefore affecting cell behavior (21).…”

Section: Introductionmentioning

confidence: 99%

Restoring HOXD10 Exhibits Therapeutic Potential for Ameliorating Malignant Progression and 5-Fluorouracil Resistance in Colorectal Cancer

Pan

Wang

et al. 2021

Front. Oncol.

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Emerging evidence suggests that hypermethylation of HOXD10 plays an important role in human cancers. However, the biological and clinical impacts of HOXD10 overmethylation and its downstream targets in colorectal cancer remain unknown. We evaluated the methylation level of HOXD10 in paired cancer and normal tissues (n = 42) by using pyrosequencing, followed by validation of the methylation status of HOXD10 from The Cancer Genome Atlas (TCGA) datasets with 302 cancer tissues and 38 normal tissues. The biological function of HOXD10 was characterized in cell lines. We further evaluated the effects of HOXD10 and its targets on chemoresistance in our established resistant cell lines and clinical cohort (n = 66). HOXD10 was found frequently methylated in colorectal cancer, and its hypermethylation correlates with its low expression level, advanced disease, and lymph node metastasis. Functionally, HOXD10 acts as a tumor suppressor gene, in which HOXD10-expressing cells showed suppressed cell proliferation, colony formation ability, and migration and invasion capacity. Mechanistically, DNMT1, DNMT3B, and MeCP2 were recruited in the HOXD10 promoter, and demethylation by 5-Aza-2′-deoxycytidine (5-Aza-CdR) treatment or MeCP2 knockdown can sufficiently induce HOXD10 expression. HOXD10 regulates the expressions of miR-7 and IGFBP3 in a promoter-dependent manner. Restoration of the expression of HOXD10 in 5-fluorouracil (5-FU)-resistant cells significantly upregulates the expressions of miR-7 and IGFBP3 and enhances chemosensitivity to 5-FU. In conclusion, we provide novel evidence that HOXD10 is frequently methylated, silenced, and contributes to the development of colorectal cancers. Restoration of HOXD10 activates the expressions of miR-7 and IGFBP3 and results in an inhibited phenotype biologically, suggesting its potential therapeutic relevance in colorectal cancer (CRC).

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Section: Introductionmentioning

confidence: 99%

Restoring HOXD10 Exhibits Therapeutic Potential for Ameliorating Malignant Progression and 5-Fluorouracil Resistance in Colorectal Cancer

Pan

Wang

et al. 2021

Front. Oncol.

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“…Sodium bisulfite conversion and sequencing works by inducing de-amination exclusively to non-methylated cytosines to produce uracil, which, when amplified by PCR, will be converted to thymine. By comparing the profile of this DNA sequence to their non-methylated original, the methylome is inferred [ 121 , 122 ]. Current variations include sequence-based analysis, interaction-based analysis and analysis based on melting temperature of the bisulphite-treated DNA.…”

Section: Dna Methylation and Painmentioning

confidence: 99%

DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain

Irfan

Febrianto

Sharma

et al. 2022

IJMS

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While about half of the population experience persistent pain associated with tissue damages during their lifetime, current symptom-based approaches often fail to reduce such pain to a satisfactory level. To provide better patient care, mechanism-based analgesic approaches must be developed, which necessitates a comprehensive understanding of the nociceptive mechanism leading to tissue injury-associated persistent pain. Epigenetic events leading the altered transcription in the nervous system are pivotal in the maintenance of pain in tissue injury. However, the mechanisms through which those events contribute to the persistence of pain are not fully understood. This review provides a summary and critical evaluation of two epigenetic mechanisms, DNA methylation and non-coding RNA expression, on transcriptional modulation in nociceptive pathways during the development of tissue injury-associated pain. We assess the pre-clinical data and their translational implication and evaluate the potential of controlling DNA methylation and non-coding RNA expression as novel analgesic approaches and/or biomarkers of persistent pain.

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“…The PI3K pathway is a well-characterised oncogenic axis (9, 10) that has been associated with drug resistance and poor prognosis (11). In head and neck region, PIK3CA is the third most commonly mutated gene (12), and the PI3K signalling is believed to be a key driver of resistance to EGFR inhibitors (13). Tumours with identical histological features may harbour different PI3K mutations.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, epigenetic heterogeneity can be often seen in the genetically identical lesions ( 4 ). Notably, promoter methylation can cause gene silencing in the absence of DNA mutations ( 14 ), leading to differential expression patterns in tumours with the same DNA sequence. For instance, the promoter of CDKN2A is frequently methylated in HNSCC and other oral cancers ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Multi-Site Tumour Sampling Improves the Detection of Intra-Tumour Heterogeneity in Oral and Oropharyngeal Squamous Cell Carcinoma

et al. 2021

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Background: Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are very common in head and neck malignancy. Intratumour heterogeneity (ITH) may hamper their responses to treatment. Hence, novel tumour sampling methods that reflect ITH are required. In this study, we investigated the clinical significance of multi-site tumour sampling (MSTS) to detect ITH in OSCC and OPSCC.Methods: One hundred eighty-two paired specimens were sampled by routine sampling (RS) or MSTS, respectively. Histologically, tumour grade, peri-tumoural vascular and lymphatic growth, perineural permeation, tumour necrosis, and muscle invasion were assessed. Immunohistochemically, the positive and average detection rates of P53(mutant), ki67 and CyclinD1 were detected. The exon 9 and exon 20 mutations of PIK3CA gene and the methylation status of the CDKN2A promoter were analysed.Results: Microscopically, the detection rate of perineural permeation, the detection density of peri-tumoural vascular and lymphatic growth, necrosis and muscle invasion in MSTS were significantly more frequent than those in RP (P < 0.05, P < 0.05, P < 0.01, P < 0.01). MSTS resulted in a higher detection rate of P53 (mutant), ki67, and CyclinD1 expression than did RS, but the difference was not significant. MSTS's detection rates in PIK3CA gene mutation and gene methylation sequencing in CDKN2A gene promoter region were both higher than RP (P < 0.05, P < 0.01). To be emphasised, the hotspot mutation H1047Rwas detected in one MSTS specimen (case 24M5) but in no RS specimens.Conclusions: This study verified that MSTS's advantage in the reflection of morphological and molecular characteristics of OSCC and OPSCC. MSTS was more representative than RP. Therefore, MSTS can compensate the RP limitations in ITH detection especially in large tumours.

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DNA methylation methods: Global DNA methylation and methylomic analyses

Cited by 122 publications

References 288 publications

Restoring HOXD10 Exhibits Therapeutic Potential for Ameliorating Malignant Progression and 5-Fluorouracil Resistance in Colorectal Cancer

Restoring HOXD10 Exhibits Therapeutic Potential for Ameliorating Malignant Progression and 5-Fluorouracil Resistance in Colorectal Cancer

DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain

Multi-Site Tumour Sampling Improves the Detection of Intra-Tumour Heterogeneity in Oral and Oropharyngeal Squamous Cell Carcinoma

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