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

Cristina Oliveira-Mateos, Anaís Sánchez-Castillo, Marta Soler, Aida Obiols-Guardia, David Piñeyro, Raquel Boque-Sastre, Maria E. Calleja-Cervantes, Manuel Castro de Moura, Anna Martínez-Cardús, Teresa Rubio, Joffrey Pelletier, Maria Martínez-Iniesta, David Herrero-Martín, Oscar M. Tirado, Antonio Gentilella, Alberto Villanueva, Manel Esteller, Lourdes Farré () and Sonia Guil ()
Additional contact information
Cristina Oliveira-Mateos: L’Hospitalet de Llobregat
Anaís Sánchez-Castillo: L’Hospitalet de Llobregat
Marta Soler: L’Hospitalet de Llobregat
Aida Obiols-Guardia: L’Hospitalet de Llobregat
David Piñeyro: L’Hospitalet de Llobregat
Raquel Boque-Sastre: L’Hospitalet de Llobregat
Maria E. Calleja-Cervantes: L’Hospitalet de Llobregat
Manuel Castro de Moura: L’Hospitalet de Llobregat
Anna Martínez-Cardús: L’Hospitalet de Llobregat
Teresa Rubio: Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat
Joffrey Pelletier: Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat
Maria Martínez-Iniesta: L’Hospitalet de Llobregat
David Herrero-Martín: L’Hospitalet de Llobregat
Oscar M. Tirado: Carlos III Institute of Health (ISCIII)
Antonio Gentilella: Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat
Alberto Villanueva: L’Hospitalet de Llobregat
Manel Esteller: L’Hospitalet de Llobregat
Lourdes Farré: L’Hospitalet de Llobregat
Sonia Guil: L’Hospitalet de Llobregat

Nature Communications, 2019, vol. 10, issue 1, 1-18

Abstract: 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.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11910-6

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DOI: 10.1038/s41467-019-11910-6

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