Oncotarget

Research Papers:

A novel oncogenic role for urokinase receptor in leukemia cells: molecular sponge for oncosuppressor microRNAs

Anna Li Santi, Anna Gorrasi, Mariaevelina Alfieri, Nunzia Montuori and Pia Ragno _

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Oncotarget. 2018; 9:27823-27834. https://doi.org/10.18632/oncotarget.25597

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Abstract

Anna Li Santi1, Anna Gorrasi1, Mariaevelina Alfieri1, Nunzia Montuori2 and Pia Ragno1

1Department of Chemistry and Biology, University of Salerno, Salerno, Italy

2Department of Translational Medical Sciences, Federico II University, Naples, Italy

Correspondence to:

Pia Ragno, email: pragno@unisa.it

Keywords: uPAR; urokinase receptor; ceRNA; AML

Received: January 16, 2018     Accepted: May 19, 2018     Published: June 12, 2018

ABSTRACT

Urokinase receptor (uPAR) expression is up-regulated and represents a negative prognostic marker in most cancers. We previously reported that uPAR and CXCR4 can be regulated by common microRNAs in leukemia cells. Transcripts containing response elements for shared microRNAs in their 3’UTR may regulate their availability.

We investigated uPAR 3’UTR capability to recruit microRNAs, thus regulating the expression of their targets. uPAR 3’UTR transfection in KG1 leukemia cells up-regulates the expression of endogenous uPAR. Transfection of uPAR 3’UTR, inserted downstream a reporter gene, increases uPAR expression and simultaneously down-regulates the reporter gene expression. Transfection of uPAR 3’UTR also increases CXCR4 expression; accordingly, uPAR silencing induces down-regulation of CXCR4 expression, through a mechanism involving Dicer, the endoribonuclease required for microRNA maturation.

Transfection of uPAR 3’UTR also increases the expression of pro-tumoral factors and modulates cell adhesion and migration, consistently with the capability of uPAR3’UTR-recruited microRNAs to target several and different transcripts and, thus, functions.

Finally, we found 3’UTR-containing variants of uPAR transcript in U937 leukemia cells, which show higher levels of uPAR expression as compared to KG1 cells, in which these variants are not detected.

These results suggest that uPAR mRNA may recruit oncosuppressor microRNAs, allowing the expression of their targets.


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