## 3 Results
### Role of lncRNAs: Focus on Sequence Conservation and Relevance of Human Homologues  
Transcriptomic analysis revealed a high number of deregulated lncRNAs (Figure 1D), suggesting that findings concerning mechanotransduction and stemness [30; 32] may also be linked to an alteration of these lncRNAs, with a high relevance for them in the regulation of cell fate. Specifically, 102 out of 357 (28%) ncDE RNAs were lncRNAs, and  
Figure 5: KEGG, Reactome, and WikiPathways enrichment analysis of co-expression modules. On the basis of the turquoise and blue modules we performed a functional enrichment analysis via the g:Profiler web tool by ranking genes according to \(\log_{2}\)FC\(\mid\). The top 10 deregulated pathways according to their significance are displayed. A significant deregulation was observed in KEGG, Reactome, and WikiPathways. KEGG (**A**,**B**) highlighted respectively 59 significantly deregulated pathways for the turquoise module and 25 for the blue one. Reactome (**C**,**D**) highlighted 151 pathways emerged as significantly deregulated for the turquoise module and 59 for the blue one. WikiPathways (**E**,**F**) highlighted 16 significant terms from turquoise module and 14 from the blue one. The \(y\)-axis represents the name of the pathway, the \(x\)-axis represents the Rich factor, dot size represents the number of different genes, and the color indicates the adjusted \(p\)-value. among them, 58% (60 out of 102 lncRNAs) were lincRNAs followed by 26% antisense RNAs (27 out of 102 lncRNAs) (Figure 1D). Moreover, we found five down-regulated lncRNAs (_2900076A07 Rik_, _Gm16892_, _Gm4262_, _Gm807_, _C130071C03 Rik_) associated to pluripotency. _2900076A07 Rik_, _Gm16892_, _Gm4262_, and _Gm807_ activation has been correlated to reprogramming of mouse fibroblasts [65], while _C130071C03 Rik_ facilitates neuronal differentiation sponging miR-101a-3p in mouse hippocampal tissue [66]. Given the importance of lncRNAs in biomedical research, we focused our attention on those that present human homologues. Specifically, when considering lincRNAs and antisense RNAs, 6 out of 87 had a human homologue, as reported in Table S3. We firstly predicted the subcellular localization for the six lncRNAs via LncLocator web-tool [54] to assess their potential function as it is well-known that lncRNAs localizing in the nucleus are often involved in regulation of gene expression and/or splicing, whereas lncRNAs exported to the cytoplasm can regulate mRNA stability and translation, protein modification, or compete for miRNAs [67]. Interestingly, four out of six lncRNAs with human homologue were predicted to locate inside the nucleus and two of them to the cytoplasm, suggesting that lncRNAs may have an influence in regulating gene expression (Tables 2 and S4, Figure S1). Then, for each of the six genes with a human homologue (e.g., _Miat_, _Linc-print_, _Mi71 Tg_, _Mir679 hg_, _C130071C03 Rik_, _Trp53 cor1_), we performed a study of their alignment with the respective human sequence and the prediction of secondary structure based on the minimum free energy (MFE) minimization (Figure S1) predicted according to [PERSON] 2004 RNA folding parameters [68] as it could reveal information about possible interaction partners and function of the transcript. Moreover, genomic location, possible co-expression, and functional annotation for lncRNAs were performed via AnnoLnc2 and are reported in Tables 2 and S4. _Miat_ is a lncRNA that may constitute a component of the nuclear matrix, located on the negative strand of chromosome 5 and predicted to localize in the nucleus. It presents two different isoforms in mice with six exons each, and four isoforms in humans, two with five exons and two with four exons, with a homology region at the 5' of the genes (Figure S1). According to the AnnoLnc2 database, it is positively correlated with 228 genes and involved in biological processes like neurogenesis and cell-cell signaling and has molecular functions like binding (Tables 2 and S4).