Characterization of GECPAR, a noncoding RNA that regulates the transcriptional program of diffuse large B-cell lymphoma

GECPAR 的表征,这是一种调节弥漫性大 B 细胞淋巴瘤转录程序的非编码 RNA

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作者:Sara Napoli, Luciano Cascione, Andrea Rinaldi, Filippo Spriano, Francesca Guidetti, Fangwen Zhang, Maria Teresa Cacciapuoti, Afua Adjeiwaa Mensah, Giulio Sartori, Nicolas Munz, Mattia Forcato, Silvio Bicciato, Annalisa Chiappella, Paola Ghione, Olivier Elemento, Leandro Cerchietti, Giorgio Inghirami

Abstract

Enhancers are regulatory regions of DNA, which play a key role in cell-type specific differentiation and development. Most active enhancers are transcribed into enhancer RNA (eRNA) that can regulate transcription of target genes by means of in cis as well as in trans action. eRNA stabilize contacts between distal genomic regions and mediate the interaction of DNA with master transcription factors. Here, we characterized an enhancer eRNA, GECPAR (germinal center proliferative adapter RNA), which is specifically transcribed in normal and neoplastic germinal center B cells from the super-enhancer of POU2AF1, a key regulatory gene of the germinal center reaction. Using diffuse large B-cell lymphoma cell line models, we demonstrated the tumor suppressor activity of GECPAR, which is mediated via its transcriptional regulation of proliferation and differentiation genes, particularly MYC and the Wnt pathway.

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