Fig 2: Protein–protein interaction (PPI) network construction and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed genes (DEGs) between HEIH/YBX3 high-expression and low-expression groups in COAD. (A) Volcano map of DEGs of HEIH expression in COAD (red: upregulation; blue: downregulation). (B) GO and KEGG pathway enrichment analyses of DEGs of HEIH in the form of a chordal graph. (C, a) Hub genes of PPI network (ranking first) and MCODE2 components identified in the gene lists. (C, b) Enrichment analysis of the hub gene network. (D, a) Hub genes of PPI network (ranking second) and MCODE2 components identified in the gene lists. (D, b) Enrichment analysis of the hub gene network. (E, a) Hub genes of PPI network (ranking third) and MCODE2 components identified in the gene lists. (E, b) Enrichment analysis of the hub gene network. (F) Volcano map of DEGs of YBX3 expression in COAD (purple: upregulation; blue: downregulation). (G) GO and KEGG pathway enrichment analyses of DEGs of YBX3 in the form of a chordal graph. (H, a) Hub genes of PPI network (ranking first) and MCODE2 components identified in the gene lists. (H, b) Enrichment analysis of the hub gene network. (I, a) Hub genes of PPI network (ranking second) and MCODE2 components identified in the gene lists. (I, b) Enrichment analysis of the hub gene network. (J, a) Hub genes of PPI network (ranking third) and MCODE2 components identified in the gene lists. (J, b) enrichment analysis of the hub gene network.

Fig 3: Top 50 genes correlated with YBX3 and HEIH expression in colon adenocarcinoma (COAD). (A) Gene co-expression heat map of the top 50 genes positively correlated with YBX3 in COAD. (B, a–e) Correlation analysis of the top five genes and YBX3 expression of COAD (positively correlated). (C) Gene co-expression heat map of the top 50 genes negatively correlated with YBX3 in COAD. (D, a–e) Correlation analysis of the top five genes and YBX3 expression of COAD (negatively correlated). (E) Gene co-expression heat map of the top 50 genes positively correlated with HEIH in COAD. (F, a–e) Correlation analysis of the top five genes and HEIH expression of COAD (positively correlated). (G) Gene co-expression heat map of the top 50 genes negatively correlated with HEIH in COAD. (H, a–e) Correlation analysis of the top five genes and HEIH expression of COAD (negatively correlated).

Fig 4: Localization, single-cell variation, and expression profile patterns of YBX3. (A) YBX3 protein topology. (B) Immunofluorescence staining of the subcellular distribution of YBX3 within the cytoplasm and nucleus of A-431, PC-3, and U-2 cell lines as adopted from the HPA database. (C) Bar plot of YBX3 mRNA expressions in diverse normal human tissues from the GTEx database. (D) Construction of YBX3-associated disease network.

Fig 5: Experimental verification of the combination and role of HEIH/YBX3 in colon cancer. (A) lncRNA HEIH pull-down. (B) Enrichment analysis of the pulled-down proteins. (C) Correlation between YBX3 expression in diverse clinical stages and prognosis in the colon cancer cohort. (D) HEIH expression level in various cancer stages quantified by qPCR. (E) YBX3 expression level in various cancer stages quantified by qPCR. (F) In SW620 cell line, lncRNA-HEIH knockdown enhanced the YBX3 expression confirmed by western blot. (G) Immunohistochemical staining of tissue microarray showing the YBX3 expression in different clinical pathological stages in magnifications of ×25, ×100, and ×200, respectively. *P<0.05; **P<0.01; ns, non-significant.