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https://www.arca.fiocruz.br/handle/icict/37085
THE TRANSCRIBED PSEUDOGENE RPSAP52 ENHANCES THE ONCOFETAL HMGA2-IGF2BP2-RAS AXIS THROUGH LIN28B-DEPENDENT AND INDEPENDENT LET-7 INHIBITION
Author
Mateos, Cristina Oliveira
Castillo, Anaís Sánchez
Soler, Marta
Guardia, Aida Obiols
Piñeyro, David
Sastre, Raquel Boque
Cervantes, Maria E. Calleja
Moura, Manuel Castro de
Cardús, Anna Martínez
Rubio, Teresa
Pelletier, Joffrey
Iniesta, Maria Martínez
Martín, David Herrero
Tirado, Oscar M.
Gentilella, Antonio
Villanueva, Alberto
Esteller, Manel
Farré, Maria de Lourdes Vallve
Guil, Sonia
Castillo, Anaís Sánchez
Soler, Marta
Guardia, Aida Obiols
Piñeyro, David
Sastre, Raquel Boque
Cervantes, Maria E. Calleja
Moura, Manuel Castro de
Cardús, Anna Martínez
Rubio, Teresa
Pelletier, Joffrey
Iniesta, Maria Martínez
Martín, David Herrero
Tirado, Oscar M.
Gentilella, Antonio
Villanueva, Alberto
Esteller, Manel
Farré, Maria de Lourdes Vallve
Guil, Sonia
Affilliation
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain / Carlos III Institute of Health. Centro de Investigación Biomédica en Red de Cáncer. Madrid, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain / Cardiff School of Biosciences. Cardiff University. Wales, UK.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Laboratory of Cancer Metabolism. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Laboratory of Cancer Metabolism. Barcelona, Catalonia, Spain.
IDIBELLL’Hospitalet de Llobregat. Program Against Cancer Therapeutic Resistance. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Sarcoma Research Group. Barcelona, Catalonia, Spain.
Carlos III Institute of Health. Centro de Investigación Biomédica en Red de Cáncer. Madrid, Spain / Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Sarcoma Research Group. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Laboratory of Cancer Metabolism. Barcelona, Catalonia, Spain / University of Barcelona. Faculty of Pharmacy. Department of Biochemistry and Physiology. Barcelona, Catalonia, Spain.
IDIBELLL’Hospitalet de Llobregat. Program Against Cancer Therapeutic Resistance.Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain / Carlos III Institute of Health. Centro de Investigación Biomédica en Red de Cáncer. Madrid, Spain / University of Barcelona. School of Medicine and Health Sciences. Physiological Sciences Department. Barcelona, Catalonia, Spain / Institució Catalana de Recerca i Estudis Avançats. Barcelona, Catalonia, Spain / Josep Carreras Leukaemia Research Institute Badalona. Barcelona, Catalonia, Spain.
IDIBELL,L’Hospitalet de Llobregat. Program Against Cancer Therapeutic Resistance.Barcelona, Catalonia, Spain / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain / Josep Carreras Leukaemia Research Institute. Badalona, Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain / Carlos III Institute of Health. Centro de Investigación Biomédica en Red de Cáncer. Madrid, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain / Cardiff School of Biosciences. Cardiff University. Wales, UK.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Laboratory of Cancer Metabolism. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Laboratory of Cancer Metabolism. Barcelona, Catalonia, Spain.
IDIBELLL’Hospitalet de Llobregat. Program Against Cancer Therapeutic Resistance. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Sarcoma Research Group. Barcelona, Catalonia, Spain.
Carlos III Institute of Health. Centro de Investigación Biomédica en Red de Cáncer. Madrid, Spain / Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Sarcoma Research Group. Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Laboratory of Cancer Metabolism. Barcelona, Catalonia, Spain / University of Barcelona. Faculty of Pharmacy. Department of Biochemistry and Physiology. Barcelona, Catalonia, Spain.
IDIBELLL’Hospitalet de Llobregat. Program Against Cancer Therapeutic Resistance.Barcelona, Catalonia, Spain.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain / Carlos III Institute of Health. Centro de Investigación Biomédica en Red de Cáncer. Madrid, Spain / University of Barcelona. School of Medicine and Health Sciences. Physiological Sciences Department. Barcelona, Catalonia, Spain / Institució Catalana de Recerca i Estudis Avançats. Barcelona, Catalonia, Spain / Josep Carreras Leukaemia Research Institute Badalona. Barcelona, Catalonia, Spain.
IDIBELL,L’Hospitalet de Llobregat. Program Against Cancer Therapeutic Resistance.Barcelona, Catalonia, Spain / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil.
Bellvitge Biomedical Research Institute. L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program. Barcelona, Catalonia, Spain / Josep Carreras Leukaemia Research Institute. Badalona, Barcelona, Catalonia, Spain.
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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