Abstract
Long non-coding RNAs are nucleotide molecules that regulate transcription in numerous cellular processes and are related to the occurrence of many diseases, including cancer. In this regard, we recently discovered a polyadenylated long non-coding RNA (named TG2-lncRNA) encoded within the first intron of the Transglutaminase type 2 gene (TGM2), which is related to tumour proliferation in human cancer cell lines. To better characterize this new biological player, we investigated the effects of its suppression in MCF-7 breast cancer cells, using siRNA treatment and RNA-sequencing. In this way, we found modifications in several networks associated to biological functions relevant for tumorigenesis (apoptosis, chronic inflammation, angiogenesis, immunomodulation, cell mobility, and epithelial–mesenchymal transition) that were originally attributed only to Transglutaminase type 2 protein but that could be regulated also by TG2-lncRNA. Moreover, our experiments strongly suggest the ability of TG2-lncRNA to directly interact with important transcription factors, such as RXRα and TP53, paving the way for several regulatory loops that can potentially influence the phenotypic behaviour of MCF-7 cells. These considerations imply the need to further investigate the relative relevance of the TG2 protein itself and/or other gene products as key regulators in the organization of breast cancer program.
Highlights
Altered functionality of TG2 leads to the onset of diseases affecting several pathways, such as functionality of TG2 leads to the onset of diseases affecting several pathways, such as fifibrosis, inflammation, and angiogenesis, and it plays a crucial role in promoting epithelial–mesenchymal transition (EMT) and brosis, inflammation, and angiogenesis, and it plays a crucial role in promoting EMT and stemness phenotype, and in regulating sensitivity to chemotherapy [15,20,21]
The TG2-lncRNA is located within the TGM2 gene, which is well-known to be associated with BrCa and is directly regulated by the same gene promoter
TG2-lncRNA in MCF-7 cancer cells revealed several molecular networks in which this long non-coding RNA is potentially involved through the regulation of key genes related to apoptosis, chronic inflammation, EMT and angiogenesis
Summary
The gene TGM2 is translated into the canonical protein transglutaminase type 2 (TG2), a multifunctional enzyme regulated by different allosteric effectors and involved in various cellular activities. It catalyses intracellular reactions of Ca2+ -dependent transamidation or of hydrolysis of GTP, as a G-protein interacting with transmembrane receptors in cell signalling, whereas outside the cell this enzyme promotes the stabilization of the ECM (Extracellular Matrix) [1,2,3,4].
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