To identify potential target genes of miR-92a-3p, we performed bioinformatics (
Supplementary Materials and Methods) and high-throughput sequencing (
Fig. 6A) analysis. First, a total of 699 common target genes were found (
Supplementary Fig. S2). Next, the top 20 Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) items of the 699 genes were significantly enriched (
Supplementary Fig. S3). The significantly enriched items for GO biological processes (BPs) were transcription, DNA-templated, positive regulation of transcription from the RNA polymerase II promoter, negative regulation of transcription from the RNA polymerase II promoter, intracellular signal transduction, and cell migration (see
Supplementary Fig. S3A). In addition, the nucleus, cytoplasm, nucleoplasm, and membrane accounted for the majority of terms of the GO cellular components (CCs; see
Supplementary Fig. S3B). The most enriched GO molecular functions (MFs) were protein binding, transcription factor activity, sequence-specific DNA binding, protein serine/threonine kinase activity, and protein kinase binding (see
Supplementary Fig. S3C). KEGG pathway enrichment analysis showed that 11 of the top 20 pathways were closely associated with angiogenesis (see
Supplementary Fig. S3D black arrow). The 11 KEGG pathways and related 63 key genes were identified (
Supplementary Table S3). Last, to further capture the relationships among the 63 key gene terms, a subset of enriched terms was selected and rendered as a network plot. We selected the terms with the best
P values from each of the 20 clusters and visualized them using Cytoscape,
20 with each node representing an enriched term and colored first by its cluster ID (
Supplementary Fig. S4A). Protein interaction enrichment analysis was applied to each Molecular Complex Detection (MCODE) component independently (see
Supplementary Fig. S4B), and the three best-scoring terms by
P values were retained as the functional description of the corresponding components (
Supplementary Table S4). Using the genes in the Regulation of Actin Cytoskeleton and the PI3K-Akt signaling pathway in combination with other studies,
17,21 three candidates were identified as associated with angiogenesis: ITGA5, PTEN, and SGK3. Additional miR-92a-3p targets include TMEM225B, NPIPA2, SULT1A4, LRRC24, CDRT4, U2AF1L5, C15orf38-AP3S2, and TMEM110-MUSTN1, predicted by high-throughput sequencing (see
Fig. 6A).