Between WT and BRAFV600E, 471 DE mRNAs (Table 3 and Supplemental Table S10) and 11 DE microRNAs (Supplemental Table S11) were indirectly validated. Gene ontology of these mRNAs demonstrated that most of the genes are also related to surface receptors involved in signal transduction and cell adhesion, but, additionally, with response to hormone stimulus and transmembrane transport (Fig. 4A). Enriched pathways (Fig. 4B) were constituted of calcium signaling pathway (Fig. 4C), cardiomyopathies and ECM-receptor interaction. KEGG enrichment pathway analysis of the validated DE microRNAs demonstrated participation of the MAPK and WNT pathways, as well as regulation of actin cytoskeleton and focal adhesion (Fig. 4D). Several pro-oncogenic genes were found to be upregulated in our analysis and were described as predicted targets of the validated DE microRNAs, as the example of MET and TGFBR1 genes (Supplemental Table S5).Table 3Top 5 upregulated and 5 downregulated DE lncRNAs between WT × BRAFV600E with examples of indirectly validated targets.Ensembllog2 FCAdj. p-valueUpregulated indirectly validated targetsDownregulated indirectly validated targetsWT × BRAF V600EWT × BRAF V600E ENSG00000255595.1 9.875.68E-05TCAP, ITGA2, LY6G6C, BEND6SLC5A5, ASTN1, PART1, IRX6 ENSG00000214797.3 5.194.92E-12HES2, DTX4, KCP, LDLRRNF157, HAP1, NWD1, SLC14A2 ENSG00000260328.1 4.042.26E-16TMPRSS4PRND, TMPRSS3, PREX2, CNTNAP2 ENSG00000230498.1 3.955.74E-14C1orf106, ADAMTS14, DMBX1, DUSP13FCGBP, GCGR, SOX3, PPP2R2C ENSG00000256916.1 3.623.51E-09ELFN2, SPTBN2, MUC16, ZNF469SSPO, ASXL3, CTNND2, CNTNAP2 ENSG00000267674.1 −8.553.89E-13VSIG1, LDLRADM2, ST3GAL6, NWD1, SLC5A8 ENSG00000237396.1 −6.353.05E-08SIGLEC6, SDK1, C1QL2, MUC21TFCP2L1, SCUBE1, SBSN, PAX1 ENSG00000227947.1 −6.225.72E-07ELFN2, EPHA10, SLC30A3, SYT1SFTPC, GATA5, SFRP1, MATN1 ENSG00000224568.1 −4.238.95E-18SLC6A14, C1orf106HIF3A, SYT13, SLC29A4, ARSF ENSG00000267214.1 −4.181.17E-06ELFN2, COL7A1, B4GALNT3FAM124A, SULT1A2, SLC29A4, CNTNAP2 Figure 4Indirectly validated targets of the DE lncRNAs between WT × BRAFV600E are involved in oncogenic pathways. (A) GO biological processes and (B) KEGG enriched pathways of the indirectly validated mRNA targets of the DE lncRNAs between WT × BRAFV600E. (C) Proteins’ network of genes linked to calcium signaling pathway, 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 WT × BRAFV600E.