miR-15a and miR-16-1 down-regulation in pituitary adenomas

J Cell Physiol. 2005 Jul;204(1):280-5. doi: 10.1002/jcp.20282.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics*
  • Adenoma / physiopathology
  • Adolescent
  • Adult
  • Aged
  • Antigens, Neoplasm
  • Arginine-tRNA Ligase / genetics
  • Down-Regulation
  • Female
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Male
  • MicroRNAs / physiology*
  • Middle Aged
  • Mitochondrial Proteins
  • Peptide Elongation Factor Tu / metabolism
  • Pituitary Gland / physiology*
  • Pituitary Neoplasms / genetics*
  • Pituitary Neoplasms / physiopathology

Substances

  • Antigens, Neoplasm
  • MicroRNAs
  • Mitochondrial Proteins
  • TUFM protein, human
  • Peptide Elongation Factor Tu
  • Arginine-tRNA Ligase