Transcription factor glucocorticoid modulatory element-binding protein 1 promotes hepatocellular carcinoma progression by activating Yes-associate protein 1

Abstract

BACKGROUND Glucocorticoid modulatory element-binding protein 1 (GMEB1), which has been identified as a transcription factor, is a protein widely expressed in various tissues. Reportedly, the dysregulation of GMEB1 is linked to the genesis and development of multiple cancers. AIM To explore GMEB1’s biological functions in hepatocellular carcinoma (HCC) and figuring out the molecular mechanism. METHODS GMEB1 expression in HCC tissues was analyzed employing the StarBase database. Immunohistochemical staining, Western blotting and quantitative real-time PCR were conducted to examine GMEB1 and Yes-associate protein 1 (YAP1) expression in HCC cells and tissues. Cell counting kit-8 assay, Transwell assay and flow cytometry were utilized to examine HCC cell proliferation, migration, invasion and apoptosis, respectively. The JASPAR database was employed for predicting the binding site of GMEB1 with YAP1 promoter. Dual-luciferase reporter gene assay and chromatin immunoprecipitation-qPCR were conducted to verify the binding relationship of GMEB1 with YAP1 promoter region. RESULTS GMEB1 was up-regulated in HCC cells and tissues, and GMEB1 expression was correlated to the tumor size and TNM stage of HCC patients. GMEB1 overexpression facilitated HCC cell multiplication, migration, and invasion, and suppressed the apoptosis, whereas GMEB1 knockdown had the opposite effects. GMEB1 bound to YAP1 promoter region and positively regulated YAP1 expression in HCC cells. CONCLUSION GMEB1 facilitates HCC malignant proliferation and metastasis by promoting the transcription of the YAP1 promoter region.