HMGA1-pseudogene7 transgenic mice develop B cell lymphomas

Marco De Martino, Davide De Biase, Floriana Forzati, Sara Carmela Credendino, Giuseppe Palma, Antonio Barbieri, Claudio Arra, Orlando Paciello, Eugenio Gaudio, Maurilio Ponzoni, Gabriella De Vita, Paolo Chieffi, Francesco Bertoni, Alfredo Fusco, Francesco Esposito

Research output: Contribution to journalArticlepeer-review

Abstract

We have recently identified and characterized two pseudogenes (HMGA1P6 and HMGA1P7) of the HMGA1 gene, which has a critical role in malignant cell transformation and cancer progression. HMGA1P6 and HMGAP17 act as microRNA decoy for HMGA1 and other cancer-related genes upregulating their protein levels. We have previously shown that they are upregulated in several human carcinomas, and their expression positively correlates with a poor prognosis and an advanced cancer stage. To evaluate in vivo oncogenic activity of HMGA1 pseudogenes, we have generated a HMGA1P7 transgenic mouse line overexpressing this pseudogene. By a mean age of 12 months, about 50% of the transgenic mice developed splenomegaly and accumulation of lymphoid cells in several body compartments. For these mice FACS and immunohistochemical analyses suggested the diagnosis of B-cell lymphoma that was further supported by clonality analyses and RNA expression profile of the pathological tissues of the HMGA1P7 transgenic tissues. Therefore, these results clearly demonstrate the oncogenic activity of HMGA1 pseudogenes in vivo.

Original languageEnglish
Article number7057
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2020

ASJC Scopus subject areas

  • General

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