title: miR-15a and miR-16-1 down-regulation in pituitary adenomas.
abstract: Micro RNAs (miRs) are small noncoding RNAs, functioning as antisense regulators of other RNAs. miR-15a and miR-16-1 genes are located at chromosome 13q14, a region which is frequently deleted in pituitary tumors. An inverse correlation has been shown in B cell chronic lymphocytic leukemia (B-CLL) between miR-15a and miR-16-1 expression and the expression levels of arginyl-tRNA synthetase (RARS), an enzyme which associates with the cofactor p43 in the aminoacyl-tRNA synthetase complex. When secreted, p43 regulates local inflammatory response and macrophage chemotaxis, and seems to have anti-neoplastic properties in mice. We explored miR-15a and miR-16-1 expression in 10 GH-secreting and in 10 PRL-secreting pituitary macroadenomas by Northern blot, and investigated the possible correlation with in vivo and in vitro characteristics. We found that miR-15a and miR-16-1 are expressed at lower levels in pituitary adenomas as compared to normal pituitary tissue. Moreover, their expression inversely correlates with tumor diameter and with RARS expression (P < 0.05), but directly correlates with p43 secretion (P < 0.02). Therefore, miR15 and miR16 down-regulation in pituitary adenomas correlates with a greater tumor diameter and a lower p43 secretion, suggesting that these genes may, at least in part, influence tumor growth.
authors.affiliation: Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies-University of Ferrara, Ferrara, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Bottoni
authors.forename: Daniela
authors.initials: D
authors.lastname: Piccin
authors.forename: Federico
authors.initials: F
authors.lastname: Tagliati
authors.forename: Andrea
authors.initials: A
authors.lastname: Luchin
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Zatelli
authors.forename: Ettore C
authors.initials: EC
authors.lastname: degli Uberti
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D001126:Arginine-tRNA Ligase / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D024101:Mitochondrial Proteins; D010444:Peptide Elongation Factor Tu / Q000378:metabolism; D010902:Pituitary Gland / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000503:physiopathology
chemical_list: D000951:Antigens, Neoplasm; D035683:MicroRNAs; D024101:Mitochondrial Proteins; C091648:TUFM protein, human; D010444:Peptide Elongation Factor Tu; D001126:Arginine-tRNA Ligase