Research Article

A Systems’ Biology Approach to Study MicroRNA-Mediated Gene Regulatory Networks

Table 3

Initial concentrations of model variables and model parameter values. Based on the experimental data, the p21-targeting miRNAs verified by Wu et al. [23] were divided into two groups: the translation repression group (marked with asterisk) and the mRNA deadenylation group. A miRNA was classified into the mRNA deadenylation group if its overexpression can result in 20% or more downregulation of the p21 mRNA level (i.e., p21 mRNA level ≤ 0.8; the basal level is 1); otherwise, it was classified into the translation repression group. For the translation repression group, only was estimated and was fixed. For the other group, both and were estimated. The initial concentrations of p21 and mp21 were set to 1, and this value was used as their basal expression levels. During the parameter estimation, the initial concentrations of p21-targeting miRNAs were set to 100, because in the publication [23] the expression levels of p21  and mp21 were measured after the individual introduction of the p21-targeting miRNAs with amount of 100 nM. Due to the lack of biological information to characterize the transcriptional activation function ( ) of p21 and its targeting miRNAs, the corresponding functions were assumed to be 1 for simplicity. The data is adapted from our previous publication [4].

Initial concentration of variables and TF functions
VariableDescriptionInitial concentration (a.u.)

p21p21 protein1
mp21p21 mRNA 1
p21-targeting miRNAs100
Complexes formed by and mp210
( )p21's transcriptional activation function1
The transcriptional activation function of 1

Fixed parameter values
ParameterDescriptionValue (hr−1)Reference

Synthesis rate constant of mp210.1155 fixed
Degradation rate constant of mp210.1155 [24]
( )Synthesis rate constant of 0.0289 fixed
( 5)Degradation rate constant of 0.0289 [25]
Synthesis rate constant of p211.3863 fixed
Degradation rate constant of p211.3863 [26]

Estimated parameter values
miRNA (state variable)
(hr−1)


(a.u. −1· hr−1)

Experimental data of p21 (protein, mRNA ± SD)

miR-298 ( )*0.11550.0254
miR-208a ( )*0.11550.0041
miR-132 ( )*0.11550.0275
miR-28-5p ( )*0.11550.0119
miR-125-5p ( )*0.11550.0018
miR-299-5p ( )*0.11550.0080
miR-345 ( )*0.11550.0051

miR-93 ( )0.15640.0235
miR-423-3p ( )0.91180.0055
miR-515-3p ( )0.20980.0253
miR-363 ( )0.22610.0399
mR-657 ( )0.34650.0158
miR-639 ( )0.43050.0327
miR-572 ( )0.30390.0360
miR-654-3p ( )9.74850.0024