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.

Implications of micro-RNA profiling for cancer diagnosis

“…Although expression differences may not necessarily reflect causal events of tumorigenesis, such changes may, nevertheless, regulate genes important in tumor pathogenesis and may be useful for classifying tumors and predicting their outcomes. Examples of such gene expression alterations in miRNAs have been detected in CLL (Calin et al, 2002), colorectal neoplasia (Michael et al, 2003;Cummins et al, 2006), pituitary adenomas (Bottoni et al, 2005), lung cancer (Takamizawa et al, 2004;Johnson et al, 2005), Burkitt's lymphoma (Metzler et al, 2004), B-cell lymphoma (Eis et al, 2005;He et al, 2005b;Kluiver et al, 2005), breast cancer , glioblastoma (Chan et al, 2005;Ciafre et al, 2005) and papillary thyroid cancer (PTC) (He et al, 2005a).…”

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer

“…DNA methylation patterns in the promoter region of the GNG7 gene were (Bottoni et al, 2005) determined by sequencing bisulphite-treated DNA. We used three paired primers for the analysis.…”

miR-195, miR-455-3p and miR-10a∗ are implicated in acquired temozolomide resistance in glioblastoma multiforme cells

“…Several miRNAs have been shown to participate in cell proliferation or apoptosis in various types of cancers. miR-15a and miR-16 have been reported to induce apoptosis by targeting BCL2 [8], and they are frequently deleted or underexpressed in chronic lymphocytic leukemia, prostate cancer and pituitary adenoma [9][10][11]. Reduced let-7 expression has been identified in lung cancer with poor prognosis [12] and inversely correlated with expression of RAS protein [13].…”