Epigenetic regulation in human melanoma: past and future

Sarkar, Debina; Leung, Euphemia; Baguley, Bruce C.; Finlay, Graeme J.; Askarian-Amiri, Marjan

doi:10.1080/15592294.2014.1003746

Cited by 246 publications

(191 citation statements)

References 167 publications

(138 reference statements)

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“…Several studies have focused on genetic alterations beside BRAF mutations, which can be involved in target therapy response; however, still little is known on the possible epigenetic regulation of the melanoma pathways [11][12][13].…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors

Pinto

Strippoli

Summa

et al. 2015

Expert Opinion on Therapeutic Targets

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Objective: Currently, the treatment of BRAF V600-mutated metastatic melanoma with BRAF inhibitors gives a response rate of ~ 50% with a progression-free survival of ~ 6 -- 7 months. In order to identify predictive biomarkers capable of stratifying BRAF-mutated patients at high risk of shorter response duration to anti-BRAF therapy, the authors analyzed the expression of 15 microRNAs (miRNAs) targeting crucial genes involved in melanoma biology and drug response.Research design and methods: A total of 15 miRNAs and target gene expression were investigated in 43 patients (30 BRAF-mutated, and 13 BRAF wild-type). Moreover, 20 BRAF-mutated patients treated with vemurafenib were analyzed for miRNA expression in respect to time-to-progression.Results: All miRNAs except miR-192 showed low expression in BRAF-mutated as compared with BRAF wild-type patients. In particular, miR-101, miR-221,miR-21, miR-338-3p and miR-191 resulted in significant downregulation inBRAF-mutated patients. Moreover, high expression of miR-192 and miR-193b* and low expression of miR-132 resulted in significant association with shorter progression.Conclusion: Three miRNAs were significantly associated with clinical outcome in metastatic melanoma patients. An increased understanding of the molecular assessment of BRAF-mutated melanomas could allow development of specific molecular tests able to predict response duration.

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Section: Discussionmentioning

confidence: 99%

“…However the molecular mechanisms underlying this very short response duration are still unknown, and although several studies on genetic alterations have been conducted to uncover predictive biomarkers, very few data are present on epigenetic regulation in melanoma [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors

Pinto

Strippoli

Summa

et al. 2015

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

show abstract

“…Both miRs and LncRNAs modulate gene expression through mechanisms that will be discussed in detail below. As both targets and enactors of A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 8 expression changes, ncRNAs are important messengers of gene regulation [60,61]. In the following sections, we outline mechanisms of ncRNAs-dependent regulation of gene expression, many of which involve traditional epigenetics.…”

Section: Defining Epigenetic Mechanismsmentioning

confidence: 99%

Non-coding RNA-mediated epigenetic regulation of liver fibrosis

et al. 2015

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“…Due to their ability to alter the expression of protein-coding oncogenes and tumor suppressor genes, miRs are proposed to have a significant role in cancer development (8). Similar to various growth-suppressive protein-encoding tumor suppressor genes, certain miR genes harbor CpG islands, which are susceptible to methylation-mediated silencing (9,10). Therefore, hypermethylation-mediated silencing of tumor-suppressive miRs may be an important mechanism of tumorigenesis (11).…”

Section: Introductionmentioning

confidence: 99%

Low folate levels are associated with methylation-mediated transcriptional repression of miR-203 and miR-375 during cervical carcinogenesis

et al. 2016

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Abstract. The aim of the present study was to investigate the correlation between a lack of folic acid and the abnormal expression of microRNA (miR)-203 and miR-375 in cervical cancer. In total, 60 tissue samples of cervical intraepithelial neoplasia (CIN) or stage IA-IIA cervical cancer (study group), and 30 samples without soluble interleukin or malignancy (control group) were examined. The expression of miR-203 and miR-375 was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the difference in expression levels was quantified using the 2 -ΔΔCq method. In addition, CaSki cervical cancer cells were cultured in vitro and treated with various concentrations of folic acid. The DNA methylation states of miR-203 and miR-375 were subsequently detected by methylation-specific PCR, and the expression levels were evaluated using RT-PCR. miR-203 and miR-375 were significantly downregulated in CIN and cervical cancer tissues, compared with the control group. There was a marked difference in terms of the expression levels of miR-375 between the two groups (P<0.05). In CaSki cells, as the concentration of folic acid increased, the positive rate of DNA methylation of miR-203 and miR-375 decreased, while the expression levels of miR-203 and miR-375 demonstrated a gradual increase, which indicated that the latter two parameters were negatively correlated (P<0.05). Compared with normal cervical tissue, the expression levels of miR-203 and miR-375 were downregulated in CIN and cervical cancer. Methylation of these two miRs was apparent in CaSki cells, and was associated with a lack of folic acid. Therefore, reduced levels of folic acid, leading to increased methylation of miR-203 and miR-375, may be significant events during cervical carcinogenesis.

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Epigenetic regulation in human melanoma: past and future

Cited by 246 publications

References 167 publications

MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors

MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors

Non-coding RNA-mediated epigenetic regulation of liver fibrosis

Low folate levels are associated with methylation-mediated transcriptional repression of miR-203 and miR-375 during cervical carcinogenesis

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