Differential expression of microRNAs during melanoma progression: miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors

Xu, Yan; Brenn, Thomas; Brown, Ewan; Doherty, V.R.; Melton, David W.

doi:10.1038/bjc.2011.568

Cited by 186 publications

(176 citation statements)

References 40 publications

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“…2B). This shows that miR-205 was down-regulated significantly in the KB oral cancer cells as well as in other cancer cells, such as melanoma Xu et al, 2012), bladder cancer , prostate carcinoma (Boll et al, 2012), endometrial cancer (Karaayvaz et al, 2012) and breast cancer (Adachi et al, 2011). These results suggest that over-expressed miR-205 would increase the level of apoptotic cell death in KB cells.…”

Section: Resultsmentioning

confidence: 50%

MicroRNA-205 Directly Regulates the Tumor Suppressor, Interleukin-24, in Human KB Oral Cancer Cells

Kim

Lee

et al. 2013

Molecules and Cells

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*MicroRNA (miRNA) is a form of small noncoding RNA that regulates the expression of genes either by inhibiting mRNA translation or by inducing its degradation. Small microRNA play important roles in regulating a large number of cellular processes, including development, proliferation and apoptosis. This study examined the biological functions of miR-205 as a tumor suppressor in KB oral cancer cells. The results showed that miR-205 expression was significantly lower in KB oral cancer cells than in human normal oral keratinocytes. Furthermore, the miR-205 over-expressed in KB oral cancer cells increased the cell cytotoxicity and induced apoptosis through the activation of caspase-3/-7. The transfection of miR-205 into KB oral cancer cells strongly induced IL-24, a well known cytokine that acts as a tumor suppressor in a range of tumor tissues. In addition, miR-205 targeted the IL-24 promoter directly to induce gene expression. Overall, miR-205 has significant therapeutic potential to turn on silenced tumor suppressor genes by targeting them with miRNA.

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Section: Resultsmentioning

confidence: 50%

MicroRNA-205 Directly Regulates the Tumor Suppressor, Interleukin-24, in Human KB Oral Cancer Cells

Kim

Lee

et al. 2013

Molecules and Cells

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“…We then sought to verify the prognostic value of miR-21, the miR200 family, and miR-205 because these had been studied by us using independent samples previously and also by others. [14][15][16][17][18][19][20][21][22][23][24][25][26] We demonstrate that miR-10b and miR-200b have independent prognostic value in a multivariable logistic regression model, raising the possibility that a miRNA panel could be used to better stratify melanoma patients than AJCC staging alone. Absence of Breslow thickness as an independent prognostic factor from the final multivariable model may reflect the fact that all of these melanomas were relatively thick, suggesting that miRNA expression may have prognostic value in this high-risk melanoma subset.…”

Section: Discussionmentioning

confidence: 82%

“…Given the large number of candidate miRNAs in the published literature, we focused on a small group of candidates that were relevant to studies published from our own laboratories. Specifically, we assessed miR-21 because we have previously analyzed this in blood 14 and other groups have found it to be relevant to melanoma, [15][16][17][18][19] and the miR200 family and mir205 because they influence EMT master regulators, about which we 20 and others [21][22][23][24][25][26] have previously published. Because these miRNAs had been previously discovered as melanoma prognostic biomarker candidates in independent experiments with different case sets, we combined the training and validation sets from the current study, and then analyzed these miRNAs in individual samples.…”

Section: Patients and Settingmentioning

confidence: 99%

microRNA-10b is a prognostic biomarker for melanoma

et al. 2016

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Malignant melanoma is an aggressive form of skin cancer. Recently, drug therapy of advanced disease has been revolutionized by new agents. More therapeutic options, coupled with the desire to extend treatment to the adjuvant setting mean that prognostic biomarkers that can be assayed from formalin-fixed paraffin-embedded clinical would be valuable. microRNAs have potential to fill this need. We analyzed 377 microRNAs in 79 primary melanomas and 32 metastases using a split sample discovery strategy. From a discovery analysis using 40 thick primary melanomas (20 cases with metastasis and 20 controls without metastasis at 5 years), microRNA expression was measured by quantitative RT-PCR (QRT-PCR). MiR-10b emerged as a candidate prognostic microRNA. This was confirmed in an independent validation set of thick primary melanomas (20 cases with metastasis and 19 controls without metastasis at 5 years). In the combined discovery and validation cohorts (n = 79), miR-10b expression showed a 3.7-fold increase in expression between cases and controls (P = 0.005) and showed a trend of increasing expression between primary melanomas and their matched metastases (Po 0.001). In situ hybridization showed expression was in melanoma cells and correlated with expression measured by QRT-PCR (P = 0.0005). We used the combined discovery and validation samples to verify the prognostic value of additional candidate microRNAs identified from other studies, and proceeded to analyze miR-200b. We demonstrated that miR-10b and miR-200b showed independent prognostic value (P = 0.002 and 0.047, respectively) in multivariable analysis alongside known clinico-pathological prognostic features (eg, Breslow thickness) using a Cox proportional hazards regression model. Furthermore, the addition of these microRNAs to the clinico-pathological features led to an improved regression model with better identification of aggressive thick melanomas. Taken together, these data suggest that miR-10b is a new prognostic microRNA for melanoma and that there could be a place for microRNA analysis in stratifying melanoma for therapy.

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“…However this reasoning is not supported by the observation that expression of the miR200 family is lost during melanoma progression ruling out their potential dominant action of ZEB2 repression, at least during melanoma progression. 42,43 As MITF depletion forces melanocytes to senescence, 39 ZEB1 may be a failsafe program for a melanoma cell to overcome the senescent state, exemplifying why ZEB1 expression in human melanoma is inversely correlated with MITF status. In this context, it is noteworthy that loss of ZEB2 in non-transformed melanocytes in vivo can result in ZEB1 misexpression, which potentially takes over in an alternative way the function of ZEB2 on the expense of differentiation.…”

Section: Discussionmentioning

confidence: 99%

Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression

et al. 2014

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Deregulation of signaling pathways that control differentiation, expansion and migration of neural crest-derived melanoblasts during normal development contributes also to melanoma progression and metastasis. Although several epithelial-tomesenchymal (EMT) transcription factors, such as zinc finger E-box binding protein 1 (ZEB1) and ZEB2, have been implicated in neural crest cell biology, little is known about their role in melanocyte homeostasis and melanoma. Here we show that mice lacking Zeb2 in the melanocyte lineage exhibit a melanoblast migration defect and, unexpectedly, a severe melanocyte differentiation defect. Loss of Zeb2 in the melanocyte lineage results in a downregulation of the Microphthalmia-associated transcription factor (Mitf) and melanocyte differentiation markers concomitant with an upregulation of Zeb1. We identify a transcriptional signaling network in which the EMT transcription factor ZEB2 regulates MITF levels to control melanocyte differentiation. Moreover, our data are also relevant for human melanomagenesis as loss of ZEB2 expression is associated with reduced patient survival. Melanocytes are specialized cells in the skin that produce melanin, a pigment that is responsible for skin and hair color and that provides protection against ultraviolet (UV) radiation. During mouse embryogenesis, melanoblasts originate from the neural crest and migrate along a dorsolateral pathway from the neural tube to the developing dermis.1 Around embryonic day (E) E11 they move into the epidermis and eventually populate the developing hair follicle.2 Here they separate into two distinct populations: the differentiated pigmented melanocytes, which reside in the hair matrix, and the non-pigmented melanocyte stem cells (MSC) in the bulge. The latter cells are responsible for replenishing the hair follicle with new melanocytes during each hair cycle. Genetic studies in mice demonstrated the importance of several key players (such as sex-determining region Y (SRY)-box 10 (Sox10), paired-box 3 (Pax3), microphthalmia-associated transcription factor (Mitf), endothelin 3/endothelin receptor B (Edn3/ Ednrb), Kitl/Kit, Slug, cellular myelocytomatosis oncogene cellular homolog (cMyc) and b-Catenin (b-Cat)) for melanoblast cell fate specification, proliferation, migration and survival.2-4 The master regulator of the melanocyte development is MITF, which is spatio-temporally controlled by several key transcription factors such as SOX10, PAX3 and b-catenin.5-7 Fundamentally, MITF induces gene expression patterns that prompt a melanocyte to differentiate and initiate pigment production by activating genes important for melanin biosynthesis (such as Tyrosinase (Tyr), Dopachrome tautomerase (Dct), Tyrosinase-related protein 1 (Tyrp1) and

show abstract

Differential expression of microRNAs during melanoma progression: miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors

Cited by 186 publications

References 40 publications

MicroRNA-205 Directly Regulates the Tumor Suppressor, Interleukin-24, in Human KB Oral Cancer Cells

MicroRNA-205 Directly Regulates the Tumor Suppressor, Interleukin-24, in Human KB Oral Cancer Cells

microRNA-10b is a prognostic biomarker for melanoma

Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression

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