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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.

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Immunodetection of target proteins and synopsis of their roles in cellular pathways and interactions with miRNAs.A, tissular lysates from control brain samples, ODGs and GBMs were analyzed by western blot with antibodies directed against the proteins indicated on the left. Equal quantities of proteins loaded on the gel were ascertained by immunodetection of beta-actin. A full length blot for detection of MDH1 is presented in supplementary Fig. S3. B, network with miRNAs and proteins. Protein names: see Table 3; EP300: E1A binding protein p300; STAT3 Ac: acetylated form of STAT3; IL6: interleukin 6; HIF-1α: hypoxia inducible factor-1alpha.
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pone-0020600-g003: Immunodetection of target proteins and synopsis of their roles in cellular pathways and interactions with miRNAs.A, tissular lysates from control brain samples, ODGs and GBMs were analyzed by western blot with antibodies directed against the proteins indicated on the left. Equal quantities of proteins loaded on the gel were ascertained by immunodetection of beta-actin. A full length blot for detection of MDH1 is presented in supplementary Fig. S3. B, network with miRNAs and proteins. Protein names: see Table 3; EP300: E1A binding protein p300; STAT3 Ac: acetylated form of STAT3; IL6: interleukin 6; HIF-1α: hypoxia inducible factor-1alpha.

Mentions: Several targets of the 26 glioma-specific miRNAs were selected and nine of them were studied because the amounts of the target proteins in tumour or control brain tissue lysates were found at a detectable level when assessed using Western blot (Fig. 3A). Detection of CD44 was also included because it has been found to be involved in miR-21 production [15] and in STAT3 activation [16].


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)

Immunodetection of target proteins and synopsis of their roles in cellular pathways and interactions with miRNAs.A, tissular lysates from control brain samples, ODGs and GBMs were analyzed by western blot with antibodies directed against the proteins indicated on the left. Equal quantities of proteins loaded on the gel were ascertained by immunodetection of beta-actin. A full length blot for detection of MDH1 is presented in supplementary Fig. S3. B, network with miRNAs and proteins. Protein names: see Table 3; EP300: E1A binding protein p300; STAT3 Ac: acetylated form of STAT3; IL6: interleukin 6; HIF-1α: hypoxia inducible factor-1alpha.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0020600-g003: Immunodetection of target proteins and synopsis of their roles in cellular pathways and interactions with miRNAs.A, tissular lysates from control brain samples, ODGs and GBMs were analyzed by western blot with antibodies directed against the proteins indicated on the left. Equal quantities of proteins loaded on the gel were ascertained by immunodetection of beta-actin. A full length blot for detection of MDH1 is presented in supplementary Fig. S3. B, network with miRNAs and proteins. Protein names: see Table 3; EP300: E1A binding protein p300; STAT3 Ac: acetylated form of STAT3; IL6: interleukin 6; HIF-1α: hypoxia inducible factor-1alpha.
Mentions: Several targets of the 26 glioma-specific miRNAs were selected and nine of them were studied because the amounts of the target proteins in tumour or control brain tissue lysates were found at a detectable level when assessed using Western blot (Fig. 3A). Detection of CD44 was also included because it has been found to be involved in miR-21 production [15] and in STAT3 activation [16].

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