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Role of miRNAs in the progression of malignant melanoma.

Mueller DW, Bosserhoff AK - Br. J. Cancer (2009)

Bottom Line: Analysis of microRNA (miRNA) biogenesis and function is an area of research that started only recently but has subsequently accelerated tremendously.This is because of the impressive impact of miRNA-mediated gene regulation and the obvious potential of those tiny RNA molecules in future diagnostic and therapeutic applications.In this review, recent progress to reveal the role of miRNAs in the tumourigenesis of malignant melanoma, as well as future prospects of melanoma-related miRNA research, will be addressed.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, Molecular Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg D-93053, Germany.

ABSTRACT
Analysis of microRNA (miRNA) biogenesis and function is an area of research that started only recently but has subsequently accelerated tremendously. This is because of the impressive impact of miRNA-mediated gene regulation and the obvious potential of those tiny RNA molecules in future diagnostic and therapeutic applications. In this review, recent progress to reveal the role of miRNAs in the tumourigenesis of malignant melanoma, as well as future prospects of melanoma-related miRNA research, will be addressed.

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Related in: MedlinePlus

Schematic representation of microRNAs (miRNAs) demonstrated to be up- or downregulated during tumourigenesis of malignant melanoma, as described in the paragraph ‘Functional characterisation of single miRNA species in melanoma cells'. miRNAs shown to be deregulated in melanoma progression by a microarray study (Mueller et al, 2009) and subsequently confirmed by qRT–PCR as described in the paragraph ‘A short history about miRNA expression profiling in malignant melanoma' are indicated by parenthesis.
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fig1: Schematic representation of microRNAs (miRNAs) demonstrated to be up- or downregulated during tumourigenesis of malignant melanoma, as described in the paragraph ‘Functional characterisation of single miRNA species in melanoma cells'. miRNAs shown to be deregulated in melanoma progression by a microarray study (Mueller et al, 2009) and subsequently confirmed by qRT–PCR as described in the paragraph ‘A short history about miRNA expression profiling in malignant melanoma' are indicated by parenthesis.

Mentions: In January 2008, a review by Molnar et al (2008) was published, in which they summarised data collected on changes in miRNA expression in solid tumours and discussed them with regard to melanoma. They underlined the potential of miRNA profiling to identify miRNAs with a prognostic value in diagnosis and the staging of malignant melanoma, as well as targets for new approaches towards therapy of this disease. The first study carrying out a detailed comparison of the miRnomes of normal human melanocytes to well-characterised melanoma cell lines derived from primary tumours and melanoma metastases was published in February 2009 (Mueller et al, 2009). In addition to melanocytes and melanoma cell lines, several model systems used for investigating important steps in melanoma development and progression were included in this work. The experimental setup of this study made it possible to identify miRNAs differentially expressed in each step of melanoma tumourigenesis, such as early development and metastasis. The most important findings can be summarised as follows: (i) expression of a high number of miRNAs is deregulated in melanoma cells compared with normal melanocytes, in which the bulk of miRNAs is upregulated in melanoma cell lines. (ii) The bulk of miRNAs deregulated most strongly was not described to be of importance in tumour development before. (iii) Heterogeneity of melanoma cells causes intrinsic changes in the expression of some miRNAs, which makes it necessary to analyse sets of cell lines/tissue samples to minimise the effects of individual alterations. Quality of data obtained was checked by carrying out a qRT–PCR analysis on some miRNAs deregulated most strongly or indicated to be involved in the progression of other cancer diseases. The expression of those miRNAs was also examined in a set of melanoma tissue samples (most of them being laser microdissected) to ensure that the observed deregulation also harbours relevance in vivo. It is interesting to note that several miRNAs, proven to harbour oncogenic or tumour-suppressive potential in other types of tumours, were found to be deregulated in malignant melanoma as well. Thus, these miRNAs may also be relevant in malignant melanoma, although the mechanisms by which they exert their function in this kind of cancer remain to be elucidated. Information about miRNAs confirmed to be deregulated during this study is included in Figure 1, which gives an overview about single miRNA species demonstrated to be deregulated in melanomagenesis.


Role of miRNAs in the progression of malignant melanoma.

Mueller DW, Bosserhoff AK - Br. J. Cancer (2009)

Schematic representation of microRNAs (miRNAs) demonstrated to be up- or downregulated during tumourigenesis of malignant melanoma, as described in the paragraph ‘Functional characterisation of single miRNA species in melanoma cells'. miRNAs shown to be deregulated in melanoma progression by a microarray study (Mueller et al, 2009) and subsequently confirmed by qRT–PCR as described in the paragraph ‘A short history about miRNA expression profiling in malignant melanoma' are indicated by parenthesis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2736818&req=5

fig1: Schematic representation of microRNAs (miRNAs) demonstrated to be up- or downregulated during tumourigenesis of malignant melanoma, as described in the paragraph ‘Functional characterisation of single miRNA species in melanoma cells'. miRNAs shown to be deregulated in melanoma progression by a microarray study (Mueller et al, 2009) and subsequently confirmed by qRT–PCR as described in the paragraph ‘A short history about miRNA expression profiling in malignant melanoma' are indicated by parenthesis.
Mentions: In January 2008, a review by Molnar et al (2008) was published, in which they summarised data collected on changes in miRNA expression in solid tumours and discussed them with regard to melanoma. They underlined the potential of miRNA profiling to identify miRNAs with a prognostic value in diagnosis and the staging of malignant melanoma, as well as targets for new approaches towards therapy of this disease. The first study carrying out a detailed comparison of the miRnomes of normal human melanocytes to well-characterised melanoma cell lines derived from primary tumours and melanoma metastases was published in February 2009 (Mueller et al, 2009). In addition to melanocytes and melanoma cell lines, several model systems used for investigating important steps in melanoma development and progression were included in this work. The experimental setup of this study made it possible to identify miRNAs differentially expressed in each step of melanoma tumourigenesis, such as early development and metastasis. The most important findings can be summarised as follows: (i) expression of a high number of miRNAs is deregulated in melanoma cells compared with normal melanocytes, in which the bulk of miRNAs is upregulated in melanoma cell lines. (ii) The bulk of miRNAs deregulated most strongly was not described to be of importance in tumour development before. (iii) Heterogeneity of melanoma cells causes intrinsic changes in the expression of some miRNAs, which makes it necessary to analyse sets of cell lines/tissue samples to minimise the effects of individual alterations. Quality of data obtained was checked by carrying out a qRT–PCR analysis on some miRNAs deregulated most strongly or indicated to be involved in the progression of other cancer diseases. The expression of those miRNAs was also examined in a set of melanoma tissue samples (most of them being laser microdissected) to ensure that the observed deregulation also harbours relevance in vivo. It is interesting to note that several miRNAs, proven to harbour oncogenic or tumour-suppressive potential in other types of tumours, were found to be deregulated in malignant melanoma as well. Thus, these miRNAs may also be relevant in malignant melanoma, although the mechanisms by which they exert their function in this kind of cancer remain to be elucidated. Information about miRNAs confirmed to be deregulated during this study is included in Figure 1, which gives an overview about single miRNA species demonstrated to be deregulated in melanomagenesis.

Bottom Line: Analysis of microRNA (miRNA) biogenesis and function is an area of research that started only recently but has subsequently accelerated tremendously.This is because of the impressive impact of miRNA-mediated gene regulation and the obvious potential of those tiny RNA molecules in future diagnostic and therapeutic applications.In this review, recent progress to reveal the role of miRNAs in the tumourigenesis of malignant melanoma, as well as future prospects of melanoma-related miRNA research, will be addressed.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, Molecular Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg D-93053, Germany.

ABSTRACT
Analysis of microRNA (miRNA) biogenesis and function is an area of research that started only recently but has subsequently accelerated tremendously. This is because of the impressive impact of miRNA-mediated gene regulation and the obvious potential of those tiny RNA molecules in future diagnostic and therapeutic applications. In this review, recent progress to reveal the role of miRNAs in the tumourigenesis of malignant melanoma, as well as future prospects of melanoma-related miRNA research, will be addressed.

Show MeSH
Related in: MedlinePlus