Predictive identification of DECs with potential ceRNA
functionality
Many prior investigations have illuminated the ability of specific
circRNAs to function as ceRNAs, binding to miRNAs in a sequence-specific
behavior and thereby inhibiting their expression or function. As such,
we next predicted the potential miRNA targets of identified DECs using
miRanda-based customized software developed by OG-Biotech based upon
known sequence complementarity between DECs and miRNAs, which then
facilitated the construction of a circRNA network incorporating 87 DECs
and their putative target miRNAs (Fig. 7). The majority of circRNAs in
this network were predicted to interact with more than 10 miRNAs, while
hsa_circ_0015733 was predicted to bind to 10 miRNAs. Notably,
hsa_circ_0005076, hsa_circ_0005044, hsa_circ_0008699,
hsa_circ_0007120, hsa_circ_0062021, hsa_circ_0000699,
hsa_circ_0002520, hsa_circ_0009130, hsa_circ_0004617,
hsa_circ_0061782, hsa_circ_0056567, hsa_circ_0040827, and
hsa_circ_0008410 were predicted to harbor binding sites for hundreds
of different miRNAs.
The potency of a given ceRNA interaction is dependent upon the number of
miRNAs, with circRNAs and miRNAs competing for target binding in a
complex intracellular environment. To identify potential
circRNA-miRNA-mRNA regulatory networks, we utilized the miRTarBase
database in conjunction with Functional MTI analysis. Cytoscape software
was used to generate six circRNA-miRNA-mRNA networks for the
RT-qPCR-validated circRNAs (Fig. 8).