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. © 2005 Wiley‐Liss, Inc.