Since the promoter region of GTSE1 harbors diverse putative binding sites, a ChIP assay was used to confirm that MTF1 and YY2, respectively, directly bind to the GTSE1 promoter in a sequence-specific manner. We further showed that either MTF1 or YY2 overexpression increased the mRNA and protein expression levels of GTSE1. In line with the present study, high expression levels of GTSE1 have been observed in lung cancer and bladder cancer.55,56 Moreover, upregulation of GTSE1 expression was positively related to advanced tumor stages, and knockdown of GTSE1 inhibited the proliferation, migration, and invasion of bladder cancer cells, exerting a similar effect on malignant progression as found in our study with glioma cells.57 Thus, MTF1 and YY2 can act as transactivators in regulating GTSE1 expression. MTF1 and YY2 are well established to function as transcription factors. MTF1 specifically binds to the promoter region on the Ins sequence and activates insulin gene transcription.58 Knockdown of YY2 decreased the level of Myc mRNA in line with the function of YY1 as an initiator-binding transcription factor on the Myc promoter.59
