Importantly, based on our modelling results, we made a hypothesis that Gata1 negatively regulates Fli1, which we validated experimentally using transcriptional assays, thus providing new insights into the dynamic nature of regulatory networks controlling differentiation of blood stem cells into erythroid cells.
However, among the target genes, the SPL and R2R3-MYB transcription factors, both of which are known to negatively regulate flavonoid biosynthesis, were experimentally validated to be targets of miR156 and miR159, respectively [ 46, 47].
GlgE is known to be negatively regulated by phosphorylation [33] and has been genetically validated as a potential drug target [34].
The use of a questionnaire that was partly newly developed and therefore not validated can have influenced the study results negatively.
A recent study experimentally validated that the TGF-beta signaling pathway negatively regulates the telomerase pathway, and other studies also reported that MDM2, which is a gene in the ATM pathway, and CTCF both inhibit the expression of telomerase [ 38- 40].
This similarity is further validated from the number of positively and negatively significant genes that are common between the two stresses, compared to the total number of positively and negatively, respectively, significant genes that are associated with each stress (see lower part of Figure 3 and Additional File 3).
We analyzed whether negatively correlated miRNA-mRNA pairs are enriched within computationally predicted and experimentally validated targets.
Some discoveries have been validated by previous research, such as miR-200 family that negatively regulates ZEB1 and ZEB2 for EMT.
NRSF, a well-documented zinc-finger repressor that negatively regulates gene expression of neuronal genes in non-neuronal cells, has >80 previously validated targets, providing a well-defined test set to define false-positive and -negative rates [ 32].
Therefore, we negatively correlated microRNA and global mRNA expression data and combined them with computationally predicted and experimentally validated targets.
