Transcription of the Human 5-Hydroxytryptamine Receptor 2B (HTR2B) Gene Is Under the Regulatory Influence of the Transcription Factors NFI and RUNX1 in Human Uveal Melanoma
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Chemistry
Molecular Biology
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Because it accounts for 70% of all eye cancers, uveal melanoma (UM) is therefore the most common primary ocular malignancy. In this study, we investigated the molecular mechanisms leading to the aberrant expression of the gene encoding the serotonin receptor 2B (HTR2B), one of the most discriminating among the candidates from the class II gene signature, in metastatic and non-metastatic UM cell lines. Transfection analyses revealed that the upstream regulatory region of the gene contains a combination of alternative positive and negative regulatory elements functional in but not in ⁺ UM cells. We demonstrated that both the transcription factors nuclear factor I (NFI) and Runt-related transcription factor I (RUNX1) interact with regulatory elements from the gene to either activate (NFI) or repress (RUNX1) expression in UM cells. The results of this study will help understand better the molecular mechanisms accounting for the abnormal expression of the HTR2B gene in uveal melanoma.
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