title: The inhibition of 45A ncRNA expression reduces tumor formation, affecting tumor nodules compactness and metastatic potential in neuroblastoma cells.
abstract: We recently reported the in vitro over-expression of 45A, a RNA polymerase III-transcribed non-coding (nc)RNA, that perturbs the intracellular content of FE65L1 affecting cell proliferation rate, short-term response to genotoxic stress, substrate adhesion capacity and, ultimately, increasing the tumorigenic potential of human neuroblastoma cells. In this work, to deeply explore the mechanism by which 45A ncRNA contributes to cancer development, we targeted in vitro and in vivo 45A levels by the stable overexpression of antisense 45A RNA.45A downregulation leads to deep modifications of cytoskeleton organization, adhesion and migration of neuroblastoma cells. These effects are correlated with alterations in the expression of several genes including GTSE1 (G2 and S phase-expressed-1), a crucial regulator of tumor cell migration and metastatic potential. Interestingly, the downregulation of 45A ncRNA strongly affects the in vivo tumorigenic potential of SKNBE2 neuroblastoma cells, increasing tumor nodule compactness and reducing GTSE1 protein expression in a subcutaneous neuroblastoma mouse model. Moreover, intracardiac injection of neuroblastoma cells showed that downregulation of 45A ncRNA also influences tumor metastatic ability. In conclusion, our data highlight a key role of 45A ncRNA in cancer development and suggest that its modulation might represent a possible novel anticancer therapeutic approach.
authors.affiliation: Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.|IRCCS-AOU San Martino-IST, Genova, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Penna
authors.affiliation: Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.|IRCCS-AOU San Martino-IST, Genova, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Gigoni
authors.affiliation: Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.|IRCCS-AOU San Martino-IST, Genova, Italy.
authors.forename: Delfina
authors.initials: D
authors.lastname: Costa
authors.affiliation: Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Vella
authors.affiliation: IRCCS-AOU San Martino-IST, Genova, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Russo
authors.affiliation: IRCCS-AOU San Martino-IST, Genova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Poggi
authors.affiliation: Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.|IRCCS-AOU San Martino-IST, Genova, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Villa
authors.affiliation: Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.|IRCCS-AOU San Martino-IST, Genova, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Brizzolara
authors.affiliation: Nanophysics Unit, Italian Institute of Technology, Morego, Genova, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Canale
authors.affiliation: Nanophysics Unit, Italian Institute of Technology, Morego, Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mescola
authors.affiliation: IRCCS-AOU San Martino-IST, Genova, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Daga
authors.affiliation: Department of Health Sciences, University of Molise, Campobasso, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Russo
authors.affiliation: Department of Internal Medicine (DIMI), University of Genova, Genova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Nizzari
authors.affiliation: Department of Internal Medicine (DIMI), University of Genova, Genova, Italy.|Center of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy.
authors.forename: Tullio
authors.initials: T
authors.lastname: Florio
authors.affiliation: IRCCS-AOU San Martino-IST, Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Menichini
authors.affiliation: Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.|IRCCS-AOU San Martino-IST, Genova, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Pagano
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004249:DNA Damage; D004260:DNA Repair; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: C115080:GTSE1 protein, human; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D016372:RNA, Antisense; D022661:RNA, Untranslated; C000626400:SNORD45A noncoding RNA, human
keywords: GTSE1; metastasis; neuroblastoma; non-coding RNA; tumorigenesis