Indirectly validated targets of the DE lncRNAs between WT × BRAFV600E tumors were demonstrated to be involved with cell surface receptors responsible for signal transduction and with cell adhesion (Fig. 4A). Pathway enrichment analysis, identified genes involved in calcium signaling and ECM-receptor interaction, which were already reported as an early transcriptome change in BRAFV600E-associated mouse model24. Interestingly, we also observed several genes correlated with cardiomyopathies that are mostly related to calcium regulation in cardiac muscle cells (Fig. 4B). Calcium (Fig. 4C) and MAPK cascade (represented by BRAFV600E group) are tightly involved, where calcium modulates the protein interaction properties of ERKs, affecting the subcellular localization and influencing the distribution of their targets47. Calcium can also stimulates MEK through Ras activation48. Therefore, these results can support a future investigation to answer if BRAFV600E-stimulated MAPK activation can be reinforced by calcium modulation induced by the DE lncRNAs. Additionally, MAPK stimulation may be supported by the indirectly validated microRNAs, since pathway analysis demonstrated an enrichment of microRNAs’ targets in cancer and MAPK pathways (Fig. 4D). Interestingly, predicted targets of the DE microRNAs were also differentially expressed in our analysis, such as the upregulation of TGFBR1 and downregulation of PRKACB (Supplemental Table S5).