Unknown,Transcriptomics,Genomics,Proteomics

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MicroRNA profiles of meningiomas


ABSTRACT: Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, usually benign and frequently associated with neurofibromatosis type 2. Here we define a human meningioma-typical miRNA profile and characterize effects of one down-regulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Up-regulation of miR-200a decreased expression of transcription factors, ZEB1 and SIP1, with consequently increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Down-regulation of miR-200a in meningiomas and arachnoidal cells resulted in increased expression of β -catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly target β -catenin mRNA, thereby inhibiting its translation and blocking β -catenin-Wnt signaling, frequently involved in cancer. A direct correlation was found between down-regulation of miR-200a and up-regulation of β-catenin in human meningioma samples. Thus, miR-200a appears to act as a multi-functional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and β -catenin-Wnt signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing insights into novel therapies for meningiomas. 14 meningioma tumor samples were compared to 3 arachnoidal tissue control samples. Two technical replicates were performed for each sample. Normalization and processing included combining the data from technical replicates. The below table contains quantile-normalized data.

ORGANISM(S): Homo sapiens

SUBMITTER: Okay Saydam 

PROVIDER: E-GEOD-17792 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Downregulated microRNA-200a in meningiomas promotes tumor growth by reducing E-cadherin and activating the Wnt/beta-catenin signaling pathway.

Saydam Okay O   Shen Yiping Y   Würdinger Thomas T   Senol Ozlem O   Boke Elvan E   James Marianne F MF   Tannous Bakhos A BA   Stemmer-Rachamimov Anat O AO   Yi Ming M   Stephens Robert M RM   Fraefel Cornel C   Gusella James F JF   Krichevsky Anna M AM   Breakefield Xandra O XO  

Molecular and cellular biology 20090824 21


Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, are usually benign, and are frequently associated with neurofibromatosis type 2. Here, we define a typical human meningioma microRNA (miRNA) profile and characterize the effects of one downregulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Upregulation of miR-200a decreased the exp  ...[more]

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