Bioinformatics analysis of regulated MicroRNAs by placental growth factor signaling in cancer stem cells

Since the effect of placental growth factor (PlGF) on MicroRNAs (miRNAs) at molecular level was remained unknown, the aim was to predict the transcription factors (TFs) and their regulated miRNAs that activated by PlGF and analysis the function, biological processes, and cancer stem cells (CSCs)-related signaling pathways of miRNAs that regulated in PlGF signaling pathway.

The aim of this study is to find the TFs that activated by PlGF, we used three online software programs PCViz, PubAngioGen, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then, the regulatory miRNAs downstream of the TFs were identified by four software TMHD, chipbase, circuits, and transmir databases. Target genes of miRNAs were predicted by three online software program TargetScan, Pictar, and miRanda algorithms. Moreover, Mirwalk database was used to find the validated miRNAs in angiogenesis process. Furthermore, Gene ontology (GO) biological process, GO molecular function, KEGG pathway, BIOCARTA pathway, Panther pathway, and Reactome pathway in Database for Annotation and Visualization and Integrated Discovery tools were used to find the functions and signaling pathways of target genes.

Many target genes of miRNAs in PlGF pathway were involved in CSCs-related signaling pathways such as Hedgehog, Wnt/b-catenin, Notch, mTOR, epidermal growth factor EGF, and transforming growth factor-beta signaling pathways. Regulatory miRNAs in PlGF signaling pathway probably promote cell proliferation, migration, tubulogenesis, and metastasize in CSCs.

Bioinformatic analysis revealed that regulatory miRNAs and their target genes in PlGF pathway played important roles in the progression of CSCs-related signaling pathways.