## 1 Introduction  
EMT is a reversible transdifferentiation process in which epithelial cells lose their characteristics and instead acquire attributes of mesenchymal cells. During EMT, cell-cell junctions are disrupted, the actin cytoskeleton is extensively reorganized and the cells acquire increased migratory and invasive characteristics [1, 2]. EMT is essential in several physiological and pathological processes, including embryonic development, wound healing, organ fibrosis and cancer progression [3]. The EMT process entails substantial changes in gene expression. Beyond the well-stablished transcriptional reprogramming during EMT, posttranscriptional mechanisms, such as regulation by alternative pre-mRNA splicing and non-coding RNA, have an important role and provide additional layers of complexity in gene regulation [4, 5, 6].  
Long non-coding RNAs (IncRNAs) are defined as RNA transcripts longer than 200 nucleotides, with no apparent protein-coding potential. More than 16,000 IncRNA genes have been identified in the human genome, on the basis of GENCODE annotations (Human GENCODE Release, v27), but only a small percentage of these have been functionally characterized. Notably, their expression is strikingly cell-type or tissue-restricted [7]. Studies on IncRNAs have demonstrated that they serve important roles in gene regulation as molecular scaffold or guides modulating nucleic acid-nucleic acid, nucleic acid-protein or protein-protein interactions, or competing endogenous RNAs that bind proteins or microRNAs (miRNAs); and as enhancers of gene expression when transcribed within enhancer regions or their neighboring loci [8; 9]. Some lncRNAs harbor miRNAs within their exonic or intronic sequences, and hence are processed to produce miRNAs that promote mRNA decay or repress target mRNAs. For example, lncRNA-H19 exon1 encodes miR-675 miRNA that suppresses the translation of the _lgf1r_ gene, inhibiting cell proliferation [10]; miR-100 and miR-125b generated from the lncRNA MiR100 HG mediate cetuximab resistance via Wnt/b-catenin signaling [11]; PVT1 lncRNA, which is processed from the MIRHG harboring the miR-1204, miR-1205, miR-1206, miR-1207-5p, miR-1207-3p and miR-1208 cluster positively regulates _c-Myc_ expression and activity [12]. A major question that needs to be answered is whether these lncRNAs are merely serving as primary miRNA units for producing miRNAs, or if they might also generate mature lncRNAs that have independent roles.  
In the present work, we studied a TGF-\(\beta\)-responsive lncRNA, we named _Lnc-Nr6a1_, expressed early during EMT. Two polyadenylated isoforms, Inc-_Nr6a1-1_ and Inc-_Nr6a1-2_, and a longer non-polyadenylated isoform were generated from _Lnc-Nr6a1_ genomic loci. The non-polyadenylated isoform contains pri-miR181a2 and pri-miR181b2 sequences, which are Dicer processed generating mature miR-181a2 and miR-181b2. We showed that migration and invasiveness of the cell increase by ectopic expression of the polyadenylated isoforms, whereas anoikis resistance increases by expression of the non-polyadenylated isoform, proving that transcripts generated from _Lnc-Nr6a1_ genomic loci perform independent functions. _Lnc-Nr6a1_ gene depletion causes defects in cell adhesion and metabolic changes that are reverted by exogenous expression of the polyadenylated Inc-_Nr6a1-1_ isoform. We demonstrated that this lncRNA isoform interacts directly with the proteins of several functional groups and serves as molecular scaffold enabling the formation of a multienzyme complex between ENO1, ALDOA, GAPDH, and PKM glycolytic enzymes, along with LDHA, and contributing to a higher level of glycolysis.