Regulation of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Protein Expression by MiR-34a in Sporadic Somatotropinomas

• DOI: 10.1371/journal.pone.0117107
• Publication Date: 2015-02-06T20:56:57Z
• Authors: Judit Dénes; Leandro Kasuki; Giampaolo Trivellin; Leandro M. Colli; Christina M. Takiya; Craig E. Stiles; Sayka Barry; Margaret de Castro; Mônica R. Gadelha; Márta Korbonits
• Keywords: HEK 293 cells; Post-transcriptional regulation; Ectopic expression

Patients with germline AIP mutations or low protein expression have large, invasive somatotroph adenomas and poor response to somatostatin analogues (SSA).To study the mechanism of 31 sporadic somatotropinomas (n = 13) high 18) were analyzed for messenger RNA (mRNA) 11 microRNAs (miRNAs) predicted bind 3'UTR AIP. Luciferase reporter assays wild-type deletion constructs AIP-3'UTR used effect selected miRNAs in GH3 cells. Endogenous mRNA levels measured after miRNA over- underexpression HEK293 cells.No significant difference was observed between tumors suggesting post-transcriptional regulation. miR-34a highly expressed samples compared inversely correlated SSA therapy. inhibited luciferase-AIP-3'UTR construct, that binds AIP-3'UTR. Deletion mutants 3 different binding sites identified c.*6-30 site be involved miR-34a's activity. overexpression cells resulted inhibition endogenous expression.Low is associated expression. can down-regulate AIP-protein but not vitro. a negative regulator could responsible an phenotype resistance SSA.