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The transcribed pseudogene RPSAP52 enhances the oncofetal HMGA2-IGF2BP2-RAS axis through LIN28B-dependent and independent let-7 inhibition

Oliveira-Mateos, Cristina, Sánchez-Castillo, Anaís, Soler, Marta, Obiols-Guardia, Aida, Piñeyro, David, Boque-Sastre, Raquel ORCID: https://orcid.org/0000-0002-0214-8848, Calleja-Cervantes, Maria E., Castro de Moura, Manuel, Martínez-Cardús, Anna, Rubio, Teresa, Pelletier, Joffrey, Martínez-Iniesta, Maria, Herrero-Martín, David, Tirado, Oscar M., Gentilella, Antonio, Villanueva, Alberto, Esteller, Manel, Farré, Lourdes and Guil, Sonia 2019. The transcribed pseudogene RPSAP52 enhances the oncofetal HMGA2-IGF2BP2-RAS axis through LIN28B-dependent and independent let-7 inhibition. Nature Communications 10 , 3979. 10.1038/s41467-019-11910-6

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Abstract

One largely unknown question in cell biology is the discrimination between inconsequential and functional transcriptional events with relevant regulatory functions. Here, we find that the oncofetal HMGA2 gene is aberrantly reexpressed in many tumor types together with its antisense transcribed pseudogene RPSAP52. RPSAP52 is abundantly present in the cytoplasm, where it interacts with the RNA binding protein IGF2BP2/IMP2, facilitating its binding to mRNA targets, promoting their translation by mediating their recruitment on polysomes and enhancing proliferative and self-renewal pathways. Notably, downregulation of RPSAP52 impairs the balance between the oncogene LIN28B and the tumor suppressor let-7 family of miRNAs, inhibits cellular proliferation and migration in vitro and slows down tumor growth in vivo. In addition, high levels of RPSAP52 in patient samples associate with a worse prognosis in sarcomas. Overall, we reveal the roles of a transcribed pseudogene that may display properties of an oncofetal master regulator in human cancers.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License.
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 1 November 2019
Date of Acceptance: 8 August 2019
Last Modified: 06 May 2023 04:33
URI: https://orca.cardiff.ac.uk/id/eprint/126472

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