Experimental evidence for such a ceRNA crosstalk has been initially shown for the tumor suppressor gene PTEN, which is regulated by the 3' untranslated region (3'UTR) of the pseudogene PTENP1 in a DICER-dependent manner.
[11] For a cooperative effect to be considered two adjacent MREs, however, have to be of miRNA families that are expressed high enough to actively repress targets and to be less than 58 nucleotides apart.
Most notably, it has been challenged by a group of researchers that performed a quantitative assessment of two miRNA families (highly and lowly expressed) and their binding sites in liver- and embryonic stem cells as described below.
[11] Due to this large number of background sites, their model suggests that prospects of observing an effect from a ceRNA are greatly reduced.
Bosia et al. used single-cell assays to demonstrate substantial ceRNA crosstalk in instances where there is a balance between binding site counts, miRNAs, and target RNA expression profiles.
[citation needed] Chiu et al. used LINCS data to support the regulation of hundreds of genes by ceRNA interactions in prostate and breast adenocarcinomas.
[21] PTEN is a critical tumor suppressor gene which is frequently altered in multiple human cancers and is a negative regulator of the oncogenic Phosphoinositide 3-kinase/Akt signaling pathway.
Three studies have identified and successfully validated protein-coding transcripts as PTEN ceRNAs in prostate cancer,[9] glioblastoma[22] and melanoma.
[25] It however still remains to be shown whether Hepatitis C can reach the high titers necessary in vivo in order to modulate gene expression through a ceRNA mechanism.
[17][26] T cells transformed by the primate virus Herpesvirus saimiri (HVS) have been shown to express viral U-rich noncoding RNAs called HSURs.
Overall, HULC lncRNA is part of a self-amplifying autoregulatory loop in which it sponges miR-372 to activate CREB, and in turn upregulates its own expression levels.
[citation needed] Bacteria do not have miRNA, and instead, ceRNAs in these organisms compete for small RNAs (sRNAs) or RNA-binding proteins (RBPs).