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Title: The transcribed pseudogene RPSAP52 enhances the oncofetal HMGA2-IGF2BP2-RAS axis through LIN28B-dependent and independent inhibition of let-7 miRNAs
Author: Oliveira-Mateos, Cristina
Sánchez-Castillo, Anaís
Soler, Marta
Obiols-Guardia, Aida
Piñeyro, David
Boque-Sastre, Raquel
Calleja Cervantes, Maria E.
Castro de Moura, Manuel
Martínez Cardús, Anna
Rubio, Teresa
Pelletier, Joffrey
Martínez Iniesta, María
Herrero Martín, David
Tirado, Oscar M.
Gentilella, Antonio
Villanueva Garatachea, Alberto
Esteller, Manel
Farré, Lourdes
Guil, Sonia
Keywords: Expressió gènica
Micro RNAs
Transducció de senyal cel·lular
Gene expression
Cellular signal transduction
Issue Date: 4-Sep-2019
Publisher: Nature Publishing Group
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.
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It is part of: Nature Communications, 2019, vol. 10, num. 1, p. 3979
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Ciències Fisiològiques)

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