Portal de Periódicos da CAPES

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

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-11910-6

2041-1723

Cristina Oliveira-Mateos, Anaís Sánchez‐Castillo, Marta Soler, Aida Obiols-Guardia, David Piñeyro, Raquel Boqué-Sastre, María Eréndira Calleja-Cervantes, Manuel Castro de Moura, Anna Martínez‐Cardús, Teresa Rubio, Joffrey Pelletier, María Martínez‐Iniesta, David Herrero‐Martín, Òscar M. Tirado, Antonio Gentilella, Alberto Villanueva, Manel Esteller, Lourdes Farré, Sònia Guil,

RNA Research and Splicing

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.