Autor: |
Bergamini CM; Department of Neuroscience and Rehabilitation, University of Ferrara, Via Luigi Borsari, 46, 44121 Ferrara, Italy., Vischioni C; Department of Animal Medicine, Health and Production, University of Padua, 35020 Legnaro, Italy., Aguiari G; Department of Neuroscience and Rehabilitation, University of Ferrara, Via Luigi Borsari, 46, 44121 Ferrara, Italy., Grandi C; Department of Biophysical Chemistry, Institute for Molecules and Materials Radboud University, HG03.344, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands., Terrazzan A; Department of Translational Medicine, University of Ferrara, Via Fossato di Mortara, 70 c.o. Viale Eliporto, 44121 Ferrara, Italy., Volinia S; Department of Translational Medicine, University of Ferrara, Via Fossato di Mortara, 70 c.o. Viale Eliporto, 44121 Ferrara, Italy., Bianchi N; Department of Translational Medicine, University of Ferrara, Via Fossato di Mortara, 70 c.o. Viale Eliporto, 44121 Ferrara, Italy., Taccioli C; Department of Animal Medicine, Health and Production, University of Padua, 35020 Legnaro, Italy. |
Abstrakt: |
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. |