title: Down-regulation of RNA editing in pediatric astrocytomas: ADAR2 editing activity inhibits cell migration and proliferation.
abstract: Since alterations in post-transcriptional events can contribute to the appearance and/or progression of cancer, we investigated whether RNA editing, catalyzed by the ADAR (adenosine deaminases that act on RNA) enzymes, is altered in pediatric astrocytomas. We find a decrease in ADAR2 editing activity that seems to correlate with the grade of malignancy in children. Despite the loss of ADAR2 editing activity in tumor tissues, the high grade astrocytomas do not exhibit alterations in ADAR2 expression when compared with their specific control tissues. However, high expression levels of ADAR1 and ADAR3 were found in tumors when compared with normal tissues dissected in the same area of the brain. We reintroduced either ADAR2 or the inactive version of ADAR2 in three astrocytoma cell lines (U118, A172, U87). The "reverted" editing status is necessary and sufficient for a significant decrease in cell malignant behavior as measured by proliferation, cell cycle, and migration assays. We show that elevated levels of ADAR1, as found in astrocytomas, do indeed interfere with ADAR2 specific editing activity. Furthermore, we show that the endogenous ADAR1 can form heterodimers with ADAR2 in astrocytes.
authors.affiliation: RNA editing Laboratory, Ospedale Pediatrico Bambino Gesù Research Institute, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cenci
authors.forename: Rita
authors.initials: R
authors.lastname: Barzotti
authors.forename: Federica
authors.initials: F
authors.lastname: Galeano
authors.forename: Sandro
authors.initials: S
authors.lastname: Corbelli
authors.forename: Rossella
authors.initials: R
authors.lastname: Rota
authors.forename: Luca
authors.initials: L
authors.lastname: Massimi
authors.forename: Concezio
authors.initials: C
authors.lastname: Di Rocco
authors.forename: Mary A
authors.initials: MA
authors.lastname: O'Connell
authors.forename: Angela
authors.initials: A
authors.lastname: Gallo
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D000293:Adolescent; D000818:Animals; D001254:Astrocytoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002648:Child; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D017393:RNA Editing; D016601:RNA-Binding Proteins
chemical_list: D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase