Mutations Suppress Cell Invasion by Activating MEG3 in Growth Hormone-secreting Pituitary Adenoma

Approximately 30%-40% of growth hormone-secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in (α subunit of stimulatory G protein). Mutations in are associated with clinical features of smaller and less invasive tumors. However, the role of mutations in the invasiveness of GHPAs is unclear. mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 () was evaluated with RT-qPCR. was manipulated in GH3 cells using a lentiviral expression system. Cell invasion ability was measured using a Transwell assay, and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by immunofluorescence and western blotting. Finally, a tumor cell xenograft mouse model was used to verify the effect of on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated compared with that in mice with wild-type . Consistently, the invasiveness of mutant -expressing GH3 cells decreased. is uniquely expressed at high levels in GHPAs harboring mutated . Accordingly, upregulation inhibited tumor cell invasion, and conversely, downregulation increased tumor cell invasion. Mechanistically, mutations inhibit EMT in GHPAs. in mutated cells prevented cell invasion through the inactivation of the Wnt/β-catenin signaling pathway, which was further validated . Our data suggest that mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the signaling pathway.