A total of 1109 DE mRNAs (Table 2 and Supplemental Table S8) and 26 DE microRNAs (Supplemental Table S9) were found to be predicted targets of the DE lncRNAs between Normal and Tumor samples and were considered as indirectly validated targets. Gene ontology and KEGG pathways enrichment of these validated mRNAs demonstrated that most of the genes are involved in surface receptors responsible for signal transduction and cell adhesion, as well as, regulation of cell death, proliferation and apoptosis (Fig. 3A). Enriched pathways (Fig. 3B) were composed of cytokine-cytokine receptor interaction, pathways in cancer (Fig. 3C), focal adhesion, MAPK pathway and calcium signaling pathway. Validated microRNAs were also used to determine enriched pathways based on their predicted targets calculated elsewhere (Fig. 3D). Genes involved in cancer and MAPK pathways were the most enriched pathways. Interestingly, some genes predicted to be targets of the validated microRNAs were also DE expressed in our analysis (Supplemental Table S2), such as upregulation of the MAPK constituents, CACNG4, CACNA1E, DUSP4, TGFBR1, FGF1, FGF2 and MAP3K1. Enriched pathways were extended to genes involved in cancer, focal adhesion and calcium signaling (Fig. 3D).Table 2Top 5 upregulated and 5 downregulated DE lncRNAs between paired Normal × Tumor with examples of indirectly validated targets.Ensembllog2 FCAdj. p-valueUpregulated indirectly validated targetsDownregulated indirectly validated targetsN × TN × T ENSG00000223914.1 7.048.69E-11VGLL1, GDF6, FAM19A2, HRH1RPS6KA5, RNF150, ANK2, FOSB ENSG00000250748.2 7.014.56E-09FUT3, GPR115, CAPN8, COL7A1SVEP1, LMOD1, DPT, KCNA1 ENSG00000214797.3 7.016.39E-09TMEM130, HES2, KCP, DTX4CDHR3, PAK3, RASSF6, NWD1 ENSG00000273132.1 5.494.17E-10KLK6, ELFN2, C19orf59, SHISA6SRF, CPXM1, LAYN, FAM163A ENSG00000230918.1 5.491.17E-10GRM4, DPP4, LRP4, SHISA6EGR1, TFCP2L1, FOXJ1, ABCA9 ENSG00000253288.1 −7.431.03E-09SLC6A20, KLK10, FUT3, HRH1HAP1, SH2D6, FOXP2, ADH1B ENSG00000272479.1 −7.191.16E-09DMBX1, TMPRSS6, TMPRSS4, PPP1R1BCUX2, PAX1, CLCNKB, FOSB ENSG00000261185.1 −6.421.13E-10B3GNT3, ELFN2, LRP4, SHISA6NR4A1, C1QTNF7, RNF150, FAM180B ENSG00000254489.1 −6.377.98E-15SYTL5, HPCAL4, KCNQ3, CPNE4RBM24, PGA3, GFRA1, RNF150 ENSG00000260412.1 −6.337.11E-09CLDN16, PDE4C, LRG1, SHROOM4SLC26A4, CDHR3, PAK3, NWD1 Figure 3Indirectly validated targets of the DE lncRNAs between N × T are involved in cancer-related processes. (A) GO biological processes and (B) KEGG enriched pathways of the indirectly validated mRNA targets of the DE lncRNAs between N × T. (C) Proteins’ network of genes linked to the pathways in cancer, where black circles are validated targets and grey circles are connective proteins. (D) KEGG Pathways enrichment of the indirectly validated microRNAs targets of the DE lncRNAs between N × T.