Limits...
MicroRNA and target protein patterns reveal physiopathological features of glioma subtypes.

Lages E, Guttin A, El Atifi M, Ramus C, Ipas H, Dupré I, Rolland D, Salon C, Godfraind C, deFraipont F, Dhobb M, Pelletier L, Wion D, Gay E, Berger F, Issartel JP - PLoS ONE (2011)

Bottom Line: Another aim of this study was to better understand glioma physiopathology looking for targets of deregulated microRNAs.We discovered that some targets of these microRNAs such as STAT3, PTBP1 or SIRT1 are differentially expressed in gliomas consistent with deregulation of microRNA expression.Understanding the connections between microRNAs and bioenergetic pathways in gliomas may lead to identification of novel therapeutic targets.

View Article: PubMed Central - PubMed

Affiliation: Team7 Nanomedicine and Brain, INSERM U836, Grenoble, France.

ABSTRACT
Gliomas such as oligodendrogliomas (ODG) and glioblastomas (GBM) are brain tumours with different clinical outcomes. Histology-based classification of these tumour types is often difficult. Therefore the first aim of this study was to gain microRNA data that can be used as reliable signatures of oligodendrogliomas and glioblastomas. We investigated the levels of 282 microRNAs using membrane-array hybridisation and real-time PCR in ODG, GBM and control brain tissues. In comparison to these control tissues, 26 deregulated microRNAs were identified in tumours and the tissue levels of seven microRNAs (miR-21, miR-128, miR-132, miR-134, miR-155, miR-210 and miR-409-5p) appropriately discriminated oligodendrogliomas from glioblastomas. Genomic, epigenomic and host gene expression studies were conducted to investigate the mechanisms involved in these deregulations. Another aim of this study was to better understand glioma physiopathology looking for targets of deregulated microRNAs. We discovered that some targets of these microRNAs such as STAT3, PTBP1 or SIRT1 are differentially expressed in gliomas consistent with deregulation of microRNA expression. Moreover, MDH1, the target of several deregulated microRNAs, is repressed in glioblastomas, making an intramitochondrial-NAD reduction mediated by the mitochondrial aspartate-malate shuttle unlikely. Understanding the connections between microRNAs and bioenergetic pathways in gliomas may lead to identification of novel therapeutic targets.

Show MeSH

Related in: MedlinePlus

Deregulated miRNAs in gliomas.Correlation between miRNA expression in ODG versus miRNA expression in GBM. Data were obtained by real-time PCR. ODG/N and GBM/N miRNA ratios are expressed in log10(ratio value). Triangles: miRNAs with a GBM/ODG ratio higher than 3 or lower than 0.33. Diagon illustrates identical expression of miRNAs in glioblastomas and oligodendrogliomas.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3105101&req=5

pone-0020600-g001: Deregulated miRNAs in gliomas.Correlation between miRNA expression in ODG versus miRNA expression in GBM. Data were obtained by real-time PCR. ODG/N and GBM/N miRNA ratios are expressed in log10(ratio value). Triangles: miRNAs with a GBM/ODG ratio higher than 3 or lower than 0.33. Diagon illustrates identical expression of miRNAs in glioblastomas and oligodendrogliomas.

Mentions: Fourteen miRNAs had high glioma to control ratios and 11 had low ratios. Only miR-210 was found in higher amounts in GBM but in lower amounts in ODG than in control tissue. The results obtained by real-time PCR were plotted on a graph that displays the ODG to control tissue miRNA ratios versus the GBM to control tissue miRNA ratios (Fig. 1). This shows that there are obviously two common sets of miRNAs that are either over-expressed or under-expressed in gliomas in comparison to the control brain tissue. In addition, six miRNAs are over-expressed in GBM compared to ODG (GBM to ODG miRNA ratios above 3 in miR-21, miR-132, miR-134, miR-155, miR-210 and miR-409-5p). On the contrary, a higher level of expression of miR-128 was found in ODG than in GBM (Table 1).


MicroRNA and target protein patterns reveal physiopathological features of glioma subtypes.

Lages E, Guttin A, El Atifi M, Ramus C, Ipas H, Dupré I, Rolland D, Salon C, Godfraind C, deFraipont F, Dhobb M, Pelletier L, Wion D, Gay E, Berger F, Issartel JP - PLoS ONE (2011)

Deregulated miRNAs in gliomas.Correlation between miRNA expression in ODG versus miRNA expression in GBM. Data were obtained by real-time PCR. ODG/N and GBM/N miRNA ratios are expressed in log10(ratio value). Triangles: miRNAs with a GBM/ODG ratio higher than 3 or lower than 0.33. Diagon illustrates identical expression of miRNAs in glioblastomas and oligodendrogliomas.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105101&req=5

pone-0020600-g001: Deregulated miRNAs in gliomas.Correlation between miRNA expression in ODG versus miRNA expression in GBM. Data were obtained by real-time PCR. ODG/N and GBM/N miRNA ratios are expressed in log10(ratio value). Triangles: miRNAs with a GBM/ODG ratio higher than 3 or lower than 0.33. Diagon illustrates identical expression of miRNAs in glioblastomas and oligodendrogliomas.
Mentions: Fourteen miRNAs had high glioma to control ratios and 11 had low ratios. Only miR-210 was found in higher amounts in GBM but in lower amounts in ODG than in control tissue. The results obtained by real-time PCR were plotted on a graph that displays the ODG to control tissue miRNA ratios versus the GBM to control tissue miRNA ratios (Fig. 1). This shows that there are obviously two common sets of miRNAs that are either over-expressed or under-expressed in gliomas in comparison to the control brain tissue. In addition, six miRNAs are over-expressed in GBM compared to ODG (GBM to ODG miRNA ratios above 3 in miR-21, miR-132, miR-134, miR-155, miR-210 and miR-409-5p). On the contrary, a higher level of expression of miR-128 was found in ODG than in GBM (Table 1).

Bottom Line: Another aim of this study was to better understand glioma physiopathology looking for targets of deregulated microRNAs.We discovered that some targets of these microRNAs such as STAT3, PTBP1 or SIRT1 are differentially expressed in gliomas consistent with deregulation of microRNA expression.Understanding the connections between microRNAs and bioenergetic pathways in gliomas may lead to identification of novel therapeutic targets.

View Article: PubMed Central - PubMed

Affiliation: Team7 Nanomedicine and Brain, INSERM U836, Grenoble, France.

ABSTRACT
Gliomas such as oligodendrogliomas (ODG) and glioblastomas (GBM) are brain tumours with different clinical outcomes. Histology-based classification of these tumour types is often difficult. Therefore the first aim of this study was to gain microRNA data that can be used as reliable signatures of oligodendrogliomas and glioblastomas. We investigated the levels of 282 microRNAs using membrane-array hybridisation and real-time PCR in ODG, GBM and control brain tissues. In comparison to these control tissues, 26 deregulated microRNAs were identified in tumours and the tissue levels of seven microRNAs (miR-21, miR-128, miR-132, miR-134, miR-155, miR-210 and miR-409-5p) appropriately discriminated oligodendrogliomas from glioblastomas. Genomic, epigenomic and host gene expression studies were conducted to investigate the mechanisms involved in these deregulations. Another aim of this study was to better understand glioma physiopathology looking for targets of deregulated microRNAs. We discovered that some targets of these microRNAs such as STAT3, PTBP1 or SIRT1 are differentially expressed in gliomas consistent with deregulation of microRNA expression. Moreover, MDH1, the target of several deregulated microRNAs, is repressed in glioblastomas, making an intramitochondrial-NAD reduction mediated by the mitochondrial aspartate-malate shuttle unlikely. Understanding the connections between microRNAs and bioenergetic pathways in gliomas may lead to identification of novel therapeutic targets.

Show MeSH
Related in: MedlinePlus