This study presents a comprehensive understanding of how Chromobox (CBX) 2 impacts tumorigenesis, progression, prognosis and chemoresistance of glioma. It was unveiled that CBX2 recruits EZH2 to modulate the levels of trimethylation on H3K27 present on the PTEN promoter, resulting in suppression of PTEN transcription and activation of AKT/mTOR signalling pathway. Here, EZH2 is linked to glioma.