Downregulation of 14q32 microRNAs in primary human desmoplastic medulloblastoma.
Medulloblastoma (MB) is one of the most common pediatric cancers, likely originating from abnormal development of cerebellar progenitor neurons. MicroRNA (miRNA) has been shown to play an important role in the development of the central nervous system. Microarray analysis was used to investigate miR...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00254/full |
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| author | Danielle Ribeiro Lucon Danielle Ribeiro Lucon Cristiane eRocha Rogério eCraveiro Dagmar eDillo Izilda A Cardinalli Denise Pontes Cavalcanti Simone dos Santos Aguiar Claudia Vianna Maurer-Morelli Jose Andres Yunes Jose Andres Yunes |
| author_facet | Danielle Ribeiro Lucon Danielle Ribeiro Lucon Cristiane eRocha Rogério eCraveiro Dagmar eDillo Izilda A Cardinalli Denise Pontes Cavalcanti Simone dos Santos Aguiar Claudia Vianna Maurer-Morelli Jose Andres Yunes Jose Andres Yunes |
| author_sort | Danielle Ribeiro Lucon |
| collection | DOAJ |
| description | Medulloblastoma (MB) is one of the most common pediatric cancers, likely originating from abnormal development of cerebellar progenitor neurons. MicroRNA (miRNA) has been shown to play an important role in the development of the central nervous system. Microarray analysis was used to investigate miRNA expression in desmoplastic MB from patients diagnosed at a young age (1 or 2 years old). Normal fetal or newborn cerebellum was used as control. A total of 84 differentially expressed miRNAs (64 downregulated and 20 upregulated) were found. Most downregulated miRNAs (32/64) were found to belong to the cluster of miRNAs at the 14q32 locus, suggesting that this miRNA locus is regulated as a module in MB. Possible mechanisms of 14q32 miRNAs downregulation were investigated by the analysis of publicly available gene expression data sets. First, expression of estrogen-related receptor γ (ESRRG), a reported positive transcriptional regulator of some 14q32 miRNAs, was found downregulated in desmoplastic MB. Second, expression of the parentally imprinted gene MEG3 was lower in MB in comparison to normal cerebellum, suggesting a possible epigenetic silencing of the 14q32 locus. miR-129-5p (11p11.2/7q32.1), miR-206 (6p12.2), and miR-323-3p (14q32.2), were chosen for functional studies in DAOY cells. Overexpression of miR-129-5p using mimics decreased DAOY proliferation. No effect was found with miR-206 or miR-323 mimics. |
| first_indexed | 2024-12-10T21:54:55Z |
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| id | doaj.art-9bd67ea7de8640e4a27d0816c22410dd |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T21:54:55Z |
| publishDate | 2013-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-9bd67ea7de8640e4a27d0816c22410dd2022-12-22T01:32:04ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2013-09-01310.3389/fonc.2013.0025461312Downregulation of 14q32 microRNAs in primary human desmoplastic medulloblastoma.Danielle Ribeiro Lucon0Danielle Ribeiro Lucon1Cristiane eRocha2Rogério eCraveiro3Dagmar eDillo4Izilda A Cardinalli5Denise Pontes Cavalcanti6Simone dos Santos Aguiar7Claudia Vianna Maurer-Morelli8Jose Andres Yunes9Jose Andres Yunes10Centro Infantil BoldriniUniversidade Estadual de CampinasUniversidade Estadual de CampinasUniversity Children´s Hospital BonnUniversity Children´s Hospital BonnCentro Infantil BoldriniUniversidade Estadual de CampinasCentro Infantil BoldriniUniversidade Estadual de CampinasCentro Infantil BoldriniUniversidade Estadual de CampinasMedulloblastoma (MB) is one of the most common pediatric cancers, likely originating from abnormal development of cerebellar progenitor neurons. MicroRNA (miRNA) has been shown to play an important role in the development of the central nervous system. Microarray analysis was used to investigate miRNA expression in desmoplastic MB from patients diagnosed at a young age (1 or 2 years old). Normal fetal or newborn cerebellum was used as control. A total of 84 differentially expressed miRNAs (64 downregulated and 20 upregulated) were found. Most downregulated miRNAs (32/64) were found to belong to the cluster of miRNAs at the 14q32 locus, suggesting that this miRNA locus is regulated as a module in MB. Possible mechanisms of 14q32 miRNAs downregulation were investigated by the analysis of publicly available gene expression data sets. First, expression of estrogen-related receptor γ (ESRRG), a reported positive transcriptional regulator of some 14q32 miRNAs, was found downregulated in desmoplastic MB. Second, expression of the parentally imprinted gene MEG3 was lower in MB in comparison to normal cerebellum, suggesting a possible epigenetic silencing of the 14q32 locus. miR-129-5p (11p11.2/7q32.1), miR-206 (6p12.2), and miR-323-3p (14q32.2), were chosen for functional studies in DAOY cells. Overexpression of miR-129-5p using mimics decreased DAOY proliferation. No effect was found with miR-206 or miR-323 mimics.http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00254/fullepigenetic14q32 miRNA clusterdesmoplatic medulloblastomaESRRGmiR-129-5pmiRNA profile |
| spellingShingle | Danielle Ribeiro Lucon Danielle Ribeiro Lucon Cristiane eRocha Rogério eCraveiro Dagmar eDillo Izilda A Cardinalli Denise Pontes Cavalcanti Simone dos Santos Aguiar Claudia Vianna Maurer-Morelli Jose Andres Yunes Jose Andres Yunes Downregulation of 14q32 microRNAs in primary human desmoplastic medulloblastoma. Frontiers in Oncology epigenetic 14q32 miRNA cluster desmoplatic medulloblastoma ESRRG miR-129-5p miRNA profile |
| title | Downregulation of 14q32 microRNAs in primary human desmoplastic medulloblastoma. |
| title_full | Downregulation of 14q32 microRNAs in primary human desmoplastic medulloblastoma. |
| title_fullStr | Downregulation of 14q32 microRNAs in primary human desmoplastic medulloblastoma. |
| title_full_unstemmed | Downregulation of 14q32 microRNAs in primary human desmoplastic medulloblastoma. |
| title_short | Downregulation of 14q32 microRNAs in primary human desmoplastic medulloblastoma. |
| title_sort | downregulation of 14q32 micrornas in primary human desmoplastic medulloblastoma |
| topic | epigenetic 14q32 miRNA cluster desmoplatic medulloblastoma ESRRG miR-129-5p miRNA profile |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00254/full |
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