Identification of DEGs in non-small cell lung cancer cells after the knockdown of HNRNPK
To determine the effects of the knockdown of HNRNPK in non-small cell lung cancer cells, we analyzed the RNA-seq data from the GEO database. A total of 594 genes were identified with a threshold of P < 0.001. The top up- and down-regulated genes were shown by the heatmap and volcano plot (Figure 1). The top ten DEGs were listed in Table 1.
Enrichment analysis of DEGs in non-small cell lung cancer cells after the knockdown of HNRNPK
To understand the potential mechanisms of HNRNPK regulating non-small cell lung cancer cells, we analyzed the KEGG and GO profiles (Figure 2). We figured out the top ten KEGG signaling pathways, including “Apelin signaling pathway”, “Oxytocin signaling pathway”, “cGMP−PKG signaling pathway”, “Parathyroid hormone synthesis, secretion and action”, “Relaxin signaling pathway”, “Dilated cardiomyopathy”, “Arrhythmogenic right ventricular cardiomyopathy”, “Peroxisome”, “GABAergic synapse”, and “Nucleotide excision repair”. We identified the top ten biological processes of GO, which contains “regulation of body fluid levels”, “steroid metabolic process”, “epithelial tube morphogenesis”, “vascular process in circulatory system”, “response to corticosteroid”, “response to glucocorticoid”, “positive regulation of protein secretion”, “negative regulation of cell−substrate adhesion”, “regulation of ketone biosynthetic process”, and “negative regulation of meiotic cell cycle”. We identified the top ten cellular components including “collagen−containing extracellular matrix”, “basement membrane”, “integral component of synaptic membrane”, “intrinsic component of synaptic membrane”, “integral component of postsynaptic membrane”, “intrinsic component of postsynaptic membrane”, “peroxisomal matrix”, “microbody lumen”, “integrin complex”, and “nucleotide−excision repair complex”. We identified the top ten molecular functions including “actin filament binding”, “extracellular matrix structural constituent”, “lyase activity”, “lipid transporter activity”, “integrin binding”, “beta−catenin binding”, “phospholipid transporter activity”, “transferase activity, transferring, sulphur−containing groups”, “intramembrane lipid transporter activity”, and “protein−membrane adaptor activity”.
PPI network and Reactome analyses
To explore the potential relationship among the DEGs, we constructed the PPI network by using 580 nodes and 1075 edges. The combined score > 0.2 was set as a cutoff by using the Cytoscape software. Table 2 indicated the top ten genes with the highest scores. The top two significant modules were presented in Figure 3. We further analyzed the PPI and DEGs with a Reactome map (Figure 4) and figured out the top ten biological processes including "Extracellular matrix organization", "NGF-stimulated transcription", "Nuclear Events (kinase and transcription factor activation)", "ROBO receptors bind AKAP5", "Integrin cell surface interactions", "Laminin interactions", "Collagen formation", "Regulation of insulin secretion", "PKA-mediated phosphorylation of key metabolic factors", and "PKA activation in glucagon signaling" (Supplemental Table S1).