Skip to main content
Fig. 6 | Journal of Experimental & Clinical Cancer Research

Fig. 6

From: GABPA-activated TGFBR2 transcription inhibits aggressiveness but is epigenetically erased by oncometabolites in renal cell carcinoma

Fig. 6

L-2-HG accumulation induces epigenetic silence of GABPA expression. A GABPA methylation is significantly higher in ccRCC tumors than in corresponding renal tissues in the TCGA cohort. B The schematic illustration of the CpG cg08521263 at the GABPA promoter. C The inverse correlation between the methylation of cg08521263 and GABPA mRNA levels in the TCGA cohort. D and E 5-AZA-treatment of A498 and 786-O cells upregulates GABPA expression coupled with the reduced methylation of cg08521263. Immunoblotting and pyrosequencing were used to assess GABPA expression and methylation, respectively. Three independent experiments were performed. F L-2-HG-treatment of A498 and 786-O cells inhibits GABPA expression. G The schematic illustration of conversion between L-2-HG and a-KG and related enzymes. H The genetic alterations in L2HGDH, MDH1/2, and LDHA/LDHB in tumors and from the TCGA ccRCC cohort and their correlation with GABPA expression. I The reduced 5-hmC accumulation in the GABPA sequence spanning cg08521263. Cells were treated with L-2-HG and ChIP assays were then carried out. J The restoration of L2HGDH expression upregulates GABPA expression coupled with increased 5-hmc and reduced methylation of cg08521263. All these effects are attenuated by addition of L-2-HG. K MDH2 depletion upregulates GABPA expression coupled with increased 5-hmc and reduced methylation of cg08521263. All these effects are attenuated by addition of L-2-HG. L LDHB depletion upregulates GABPA expression coupled with increased 5-hmc and reduced methylation of cg08521263. All these effects are attenuated by addition of L-2-HG. Three independent experiments were performed. *, ** and *** denote P < 0.05, 0.01 and 0.001, respectively

Back to article page