Functional enrichment analyses on the parental genes of DECs
Both circRNAs and mRNAs are derived from shared pre-mRNA precursors, so we next explored the functional roles of the parental genes sequences from which these DECs were derived using the ClusterProfiler tool to conduct GO and KEGG enrichment analyses for the 127 DECs (four intergenic circRNAs had been excluded from this analysis).
The top 30 GO terms enriched by these DECs were compiled in Figure 3A. Significant biological process terms included B cell homeostasis (GO:0001782), lymphocyte homeostasis (GO:0002260), leukocyte homeostasis (GO:0001776), RNA phosphodiester bond hydrolysis, endonucleolytic (GO:0090502), homeostasis of number of cells (GO:0048872), small GTPase mediated signal transduction (GO:0007264), positive regulation of GTPase activity (GO:0043547), antigen receptor-mediated signaling pathway (GO:0050851), sister chromatid cohesion (GO:0007062), B cell receptor signaling pathway (GO:0050853), covalent chromatin modification (GO:0016569), regulation of small GTPase mediated signal transduction (GO:0051056), regulation of GTPase activity (GO:0043087), RNA phosphodiester bond hydrolysis (GO:0090501), chromosome organization (GO:0051276), chromosome segregation (GO:0007059), nucleocytoplasmic transport (GO:0006913), nuclear transport (GO:0051169), chromatin organization (GO:0006325), and protein polymerization (GO:0051258). Top enriched cellular component terms included Golgi-associated vesicle membrane (GO:0030660), Golgi-associated vesicle (GO:0005798), nuclear speck (GO:0016607), nuclear body (GO:0016604), lytic vacuole (GO:0000323), lysosome (GO:0005764), cytosol (GO:0005829), chromatin (GO:0000785), vacuole (GO:0005773), lysosomal membrane (GO:0005765), spindle (GO:0005819), intracellular membrane-bounded organelle (GO:0043231), nucleoplasm (GO:0005654), vacuolar membrane (GO:0005774), cytoplasm (GO:0005737), intracellular ribonucleoprotein complex (GO:0030529), ribonucleoprotein complex (GO:1990904), intracellular organelle (GO:0043229), and cytoplasmic region (GO:0099568). Moreover, top molecular function terms included GTPase activator activity (GO:0005096), endoribonuclease activity (GO:0004521), GTPase regulator activity (GO:0030695), organic cyclic compound binding (GO:0097159), ribonuclease activity (GO:0004540), RNA binding (GO:0003723), enzyme activator activity (GO:0008047), ubiquitin-protein transferase activity (GO:0004842), ubiquitin-like protein transferase activity (GO:0019787), endonuclease activity (GO:0004519), Ras GTPase binding (GO:0017016), Rab GTPase binding (GO:0017137), nucleic acid binding (GO:0003676), small GTPase binding (GO:0031267), enzyme regulator activity (GO:0030234), kinase binding (GO:0019900), molecular function regulator (GO:0098772), GTPase binding (GO:0051020), protein serine/threonine kinase activity (GO:0004674), protein kinase activity (GO:0004672), tubulin binding (GO:0015631), purine ribonucleoside triphosphate binding (GO:0035639), cytoskeletal protein binding (GO:0008092), nuclease activity (GO:0004518), and transferase activity (GO:0016740).
KEGG enrichment analysis was conducted and led to the identification of 143 pathway terms, 44 of which were found to be significantly enriched by these DEC parental genes (P <0.05). The top 30 enriched pathways were compiled in Fig. 3B, mainly including the ErbB signaling (hsa04012), Phospholipase D signaling (hsa04072), Gap junction (hsa04540), GnRH signaling (hsa04912), Choline metabolism in cancer (hsa05231), Endocrine and other factor-regulated calcium reabsorption (hsa04961), T cell receptor signaling (hsa04660), B cell receptor signaling (hsa04662), Thyroid hormone synthesis (hsa04918), Gastric acid secretion (hsa04971), Bacterial invasion of epithelial cells (hsa05100), Chronic myeloid leukemia (hsa05220), mTOR signaling (hsa04150), Ras signaling (hsa04014), EGFR tyrosine kinase inhibitor resistance (hsa01521), and Oxytocin signaling (hsa04921) pathways.