MEG3 is associated with gsp oncogene regulation of growth hormone hypersecretion, proliferation and invasiveness of human GH‑secreting adenomas

Overactivation of the Gs-mediated pathway by mutations of the G-protein α subunit (Gsα), a gsp oncogene, results in increased growth hormone (GH) hypersecretion and reduced tumor volume in patients with GH-secreting pituitary tumors. However, the mechanism underlying the clinical characteristics of gsp oncogene requires further investigation. Cyclic adenosine monophosphate-responsive element binding (CREB), as a downstream target gene of gsp oncogene, is implicated in activating maternally expressed gene 3 (MEG3). The present study proposes that gsp oncogene mediates MEG3-regulating GH hypersecretion, resulting in the small tumor size of GH-secreting tumors. Therefore, the present study detected Gsα mutations by polymerase chain reaction in GH-secreting tumors, and revealed that Gsα mutations were observed in 7/25 (28%) GH-secreting tumors. Gsp-positive tumors indicated significantly increased levels of phosphorylated p-CREB (P