## 3 Discussion
As has been described for other miRNA-host IncRNAs [11; 22; 25], _Inc-Nr6a1_ carries out specific functions that are independent of its role as a miRNA precursor, thus the loss of adhesion capacity shown by _Inc-Nr6a1_-depleted cells is rescued by exogenous expression of the Inc-_Nr6a1-1_ isoform; in the same way, the glycolytic activity in _Inc-Nr6a1_-depleted cells reaches levels similar to those of the control cells when overexpressing the Inc-_Nr6a1-1_ isoform; and also, overexpression of any of the polyadenylated isoforms increases cell mobility and invasiveness. However, anoikis resistance only increases when miR-181a2 and miR-181b2 are expressed. Therefore, the _Inc-Nr6a1_ gene, in addition to providing miR-181a2/b2 molecules, generates polyadenylated IncRNA molecules with independent functions. The in vivo study of proteins interacting with the Inc-_Nr6a1-1_ isoform reveals that this isoform interacts with different proteins, some of them participating in the same process or mechanism, suggesting that Inc-_Nr6a1-1_ could act as a scaffold molecule by recruiting or titrating the interacting proteins. Lamin A/C is the most enriched Inc-_Nr6a1-1_-interacting protein. Lamin A/C is a structural component of the nuclear lamina that regulates genome organization and gene expression. Lamin A/C associates with chromatin through large domains termed lamina-associated domains or LADs, which are located at the nuclear periphery [26]; however, Inc-_Nr6a1-1_ does not interact with DNA. Therefore, its interaction with Lamin A/C would take place in regions where Lamin A/C does not interact with DNA, such as the nucleoplasm, where significant levels of A-type lamins have been found [27]. The LADs present in the cell change as gene expression changes; however, in _Inc-Nr6a1_-depleted cells only partial changes in LADs are detected, which do not correspond to gene expression changes detected in the _Inc-Nr6a1_-depleted cells. This would indicate that Inc-_Nr6a1-1_ carries out functions in the nucleus, unknown at the moment, but it would not act as a transcriptional regulator. Inc-_Nr6a1-1_ interacts directly with the proteins plakophilin, plakoglobin and desmoplakin; the three main components of the desmosome [28]. Desmoplakin couples intermediate filaments to the desmosome and its amino-terminus binds directly to plakoglobin and the plakophilin [29]. The direct interaction of Inc-_Nr6a1-1_ with these proteins marks it as an additional component of the desmosome that could facilitate the formation of the complex. This could explain the cell-cell adhesion decrease in _Inc-Nr6a1_-depleted cells and subsequent recovery after exogenous expression of the Inc-_Nr6a1-1_ isoform. It is increasingly evident that glycolysis proteins associate to form multienzyme complexes, especially under stress conditions to meet excessive energy demand. Studies on yeast have revealed that glycolysis enzymes colocalize into non-membrane-bound granules, named glycolytic bodies or G bodies, in response to hypoxia [30]; also, in neurons of _Caenorhabditis elegans_, analogous granules are formed to sustain changes in the activity of synapses [31]. These structures are formed by phase separation and RNA molecules appear to be responsible for concentrating and sequestering protein components through multiple binding sites [32; 33]. A large number of studies have shown that lncRNAs can affect genes involved in glucose metabolism by directly regulating the glycolytic enzymes and glucose transporters or indirectly modulating the signaling pathways [34]. We have found that ENO1, ALDOA, GAPDH, and PKM glycolytic enzymes, along with LDHA, interact in vivo directly with Inc-_Nr6a1-1_ isoform in non-transformed NMuMG cells in normal conditions. Glycolytic metabolism is affected in _Luc-Nr6a1_-depleted cells; thus, these cells showed lower basal and reserve glycolytic activity than control cells; but the glycolytic activity was recovered upon exogenous expression of the Inc-_Nr6a1-1_ isoform.