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The tumor suppressor gene rap1GAP is silenced by mir-101-mediated EZH2 overexpression in invasive squamous cell carcinoma

ABSTRACT: Rap1GAP is a critical tumor suppressor gene that is down-regulated in multiple aggressive cancers such as head and neck squamous cell carcinoma, melanoma and pancreatic cancer. However, the mechanistic basis of rap1GAP down-regulation in cancers is poorly understood. By employing an integrative approach, we demonstrate polycomb-mediated repression of rap1GAP that involves EZH2, a histone methyltransferase in head and neck cancers. We further concomitant down-regulation of rap1GAP in head and neck cancers. EZH2 represses rap1GAP by facilitating the trimethylation of H3K27, a mark of gene repression, and also hypermethylation of rap1GAP promoter. These results provide a conceptual framework involving a microRNA-oncogene-tumor suppressor axis to understand head and neck cancer progression. OSCC3-siRNA Non-Targeting Vs. siRNA EZH2 with dye-swap, HOK-Adeno CMV Vs. Adeno EZH2.

ORGANISM(S): Homo sapiens

SUBMITTER: NISHA D'SILVA 

PROVIDER: E-GEOD-28501 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The tumor suppressor gene rap1GAP is silenced by miR-101-mediated EZH2 overexpression in invasive squamous cell carcinoma.

Banerjee R R   Mani R-S RS   Russo N N   Scanlon C S CS   Tsodikov A A   Jing X X   Cao Q Q   Palanisamy N N   Metwally T T   Inglehart R C RC   Tomlins S S   Bradford C C   Carey T T   Wolf G G   Kalyana-Sundaram S S   Chinnaiyan A M AM   Varambally S S   D'Silva N J NJ  

Oncogene 20110502 42

Rap1GAP is a critical tumor suppressor gene that is downregulated in multiple aggressive cancers, such as head and neck squamous cell carcinoma, melanoma and pancreatic cancer. However, the mechanistic basis of rap1GAP downregulation in cancers is poorly understood. By employing an integrative approach, we demonstrate polycomb-mediated repression of rap1GAP that involves Enhancer of Zeste Homolog 2 (EZH2), a histone methyltransferase in head and neck cancers. We further demonstrate that the loss  ...[more]

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