LncRNA growth arrest specific transcript 5 inhibits the growth of pituitary neuroendocrine tumors via miR-27a-5p/cylindromatosis axis

Abstract

ABSTRACT The long noncoding RNA growth arrest-specific transcript 5 (GAS5) has been reported to function as a suppressor in many cancers. However, the role and mechanism of lncRNA GAS5 in pituitary neuroendocrine tumors (PitNETs) remain unclear. Here, we found that lncRNA GAS5 and cylindromatosis (CYLD) expression was downregulated in invasive PitNET tissues and was negatively correlated with miR-27a-5p expression. LncRNA GAS5 overexpression inhibited proliferation of PitNETs cell line MMQ and GH3 cells and induced cell apoptosis, simultaneously, inhibited miR-27a-5p expression and increased CYLD expression. Moreover, miR-27a-5p mimic significantly decreased the luciferase activities of lncRNA GAS5 and CYLD luciferase reporter vector and downregulated CYLD expression, while miR-27a-5p inhibitor increased the expression of CYLD in MMQ and GH3 cells. Furthermore, RNA-immunoprecipitation assay revealed the direct binding between lncRNA GAS5 and miR-27a-5p. Additionally, miR-27a-5p mimic or silenced CYLD attenuated the effect of lncRNA GAS5 on MMQ and GH3 cell proliferation. In vivo lncRNA GAS5 overexpression inhibited GH3 cell tumor growth, while miR-27a-5p mimic or silenced CYLD attenuated the effect of lncRNA GAS5 on GH3 cell tumor growth. These results suggest that lncRNA GAS5 acts as an endogenous sponge by binding miR-27a-5p to increase the expression of its target gene CYLD, thereby inhibits PitNETs cell proliferation and tumor growth.