@Article{or.2024.046007,
AUTHOR = {CHAO TANG, CHUNYU ZHONG, JUNHAO ZHU, FENG YUAN, JIN YANG, YONG XU, CHIYUAN MA},
TITLE = {<i>GNAS</i> mutations suppress cell invasion by activating MEG3 in growth hormone–secreting pituitary adenoma},
JOURNAL = {Oncology Research},
VOLUME = {32},
YEAR = {2024},
NUMBER = {6},
PAGES = {1079--1091},
URL = {http://www.techscience.com/or/v32n6/56594},
ISSN = {1555-3906},
ABSTRACT = {Approximately 30%–40% of growth hormone–secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in <i>GNAS</i> (α subunit of stimulatory G protein). Mutations in <i>GNAS</i> are associated with clinical features of smaller and less invasive tumors. However, the role of <i>GNAS</i> mutations in the invasiveness of GHPAs is unclear. <i>GNAS</i> mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 (<i>MEG3</i>) was evaluated with RT-qPCR. <i>MEG3</i> 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 <i>MEG3</i> on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated <i>GNAS</i> compared with that in mice with wild-type <i>GNAS</i>. Consistently, the invasiveness of mutant <i>GNAS</i>-expressing GH3 cells decreased. <i>MEG3</i> is uniquely expressed at high levels in GHPAs harboring mutated <i>GNAS</i>. Accordingly, <i>MEG3</i> upregulation inhibited tumor cell invasion, and conversely, <i>MEG3</i> downregulation increased tumor cell invasion. Mechanistically, <i>GNAS</i> mutations inhibit EMT in GHPAs. <i>MEG3</i> in mutated <i>GNAS</i> cells prevented cell invasion through the inactivation of the Wnt/β-catenin signaling pathway, which was further validated <i>in vivo</i>. Our data suggest that <i>GNAS</i> mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the <i>MEG3/Wnt/β-catenin</i> signaling pathway.},
DOI = {10.32604/or.2024.046007}
}