Identification of uPAR Variants Acting as ceRNAs in Leukaemia Cells

Abstract

The 3′untranslated region (3′UTR) of the urokinase (uPA) receptor (uPAR) mRNA can act as a competitive endogenous RNA (ceRNA) in acute myeloid leukaemia (AML) cells, promoting the expression of pro-tumoral targets, including uPAR. Here, we identified three variants of uPAR mRNA containing the 3′UTR, in KG1 and U937 leukaemia cells expressing low and high uPAR levels, respectively. Identified variants lack exon 5 (uPAR Δ5) or exon 6 (uPAR Δ6) or part of exon 6, exon 7 and part of 3′UTR (uPAR Δ6/7). uPAR Δ5 and uPAR Δ6 transcript levels were higher in U937 cells compared to KG1 cells. Both uPAR variants were expressed also in AML blasts, at higher levels as compared to CD34 hematopoietic cells from healthy donors. The presence of the 3′UTR conferred high instability to the uPAR Δ5 variant transcript, preventing its translation in protein. Overexpression of the uPAR Δ5-3′UTR variant regulated the expression of some pro-tumoral factors previously reported to be regulated by the 3′UTR of uPAR and increased KG1 cell adhesion, migration and proliferation. These results demonstrate the expression of uPAR mRNA variants containing the 3′UTR in AML cells and the ceRNA activity and the biological effects of the uPAR Δ5-3′UTR variant.

Posttranscriptional Regulation of the Plasminogen Activation System by Non-Coding RNA in Cancer

“…The most abundant variant, lacking exon 5 (uPAR Δ5), has been cloned and transfected in AML KG1 cells. The presence of the 3′UTR conferred high instability to the uPAR Δ5 variant transcript, preventing its translation in protein; at the same time, its overexpression regulated the expression of some pro-tumoral factors previously reported to be regulated by the 3′UTR of uPAR, confirming its ceRNA activity, and increased transfected cell adhesion, migration and proliferation [ 77 ].…”