Format

Send to

Choose Destination
Nat Commun. 2019 Sep 4;10(1):3979. doi: 10.1038/s41467-019-11910-6.

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

Author information

1
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain.
2
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Carlos III Institute of Health (ISCIII), Madrid, Spain.
3
Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, Wales, UK.
4
Laboratory of Cancer Metabolism, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain.
5
Program Against Cancer Therapeutic Resistance (ProCURE), ICO, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain.
6
Sarcoma Research Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain.
7
Department of Biochemistry and Physiology, Faculty of Pharmacy, University of Barcelona (UB), Barcelona, Catalonia, Spain.
8
Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, Spain.
9
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
10
Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain.
11
Program Against Cancer Therapeutic Resistance (ProCURE), ICO, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain. mfarre@idibell.cat.
12
Laboratory of Experimental Pathology (LAPEX), Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (CPQGM/FIOCRUZ), Salvador, Bahia, Brazil. mfarre@idibell.cat.
13
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain. sguil@carrerasresearch.org.
14
Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain. sguil@carrerasresearch.org.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center