Silencing of the Imprinted DLK1-MEG3 Locus in Human Clinically Nonfunctioning Pituitary Adenomas

• DOI: 10.1016/j.ajpath.2011.07.002
• Publication Date: 2011-08-25T21:01:00Z
• Authors: Pornsuk Cheunsuchon; Yunli Zhou; Xun Zhang; Hang Lee; Wendy Chen; Yuki Nakayama; Kimberley A. Rice; E. Tessa Hedley-W...; Brooke Swearingen; Anne Klibanski
• Keywords: MEG3; Genomic Imprinting

DLK1-MEG3 is an imprinted locus consisting of multiple maternally expressed noncoding RNA genes and paternally protein-coding genes. The expression gene 3 (MEG3) selectively lost in clinically nonfunctioning adenomas (NFAs) gonadotroph origin; however, status other at this human pituitary has not previously been reported. Using quantitative real-time RT-PCR, we evaluated 24 from the 44 (25 NFAs, 7 ACTH-secreting, GH-secreting, 5 PRL-secreting adenomas) 10 normal pituitaries. effects on cell proliferation five miRNAs whose was NFAs were investigated by flow cytometry analysis. We found that 18 genes, including 13 locus, significantly down-regulated NFAs. In ACTH-secreting adenomas, 12 down-regulated, respectively; no GH-secreting tumors. One tested induced cycle arrest G2/M phase PDFS cells derived a NFA. Our data indicate silenced growth suppression consistent with hypothesis plays tumor suppressor role