Fig. 7: Blocking PHGDH methylation with a synthesized nonmethylated peptide inhibits HCC growth. | Nature Communications

Fig. 7: Blocking PHGDH methylation with a synthesized nonmethylated peptide inhibits HCC growth.

From: PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma

Fig. 7

a The aa sequence of the TAT-methylated and TAT-nonmethylated peptides. b, c Endogenous PHGDH was immunoprecipitated in Huh7 and PLC/PRF/5 cells treated with the methylated or nonmethylated peptides (20 μM) for 24 h. Immunoblotting was performed with indicated antibodies (b). PHGDH activity was measured and normalized to PHGDH protein (c). Data in c are presented as the mean ± SD (n  =  3 independent experiments). Statistical analysis was performed using the two-tailed Student’s t test. d, e Total serine (d) and glycine (e) levels in cells grown in -SG medium with treatment of the methylated or nonmethylated peptides (20 μM) for 24 h. Data are presented as the mean ± SD (n  =  3 independent experiments). Statistical analysis was performed using the two-tailed Student’s t-test. f Growth rates of Huh7 and PLC/PRF/5 cells grown in CM or -SG medium with treatment of the methylated or nonmethylated peptides (20 μM). Data are presented as the mean ± SD (n  =  5 independent experiments). Statistical analysis was performed using the two-way ANOVA with Bonferroni correction. g–i Images (g), weight (h), and volume (i) of HCC PDX tumors from mice fed with a -SG diet and treated with the methylated or nonmethylated peptides. Data are presented as the mean ± SD (n = 6 mice). Statistical analysis in h was performed using the two-tailed Student’s t test, and statistical analysis in i was performed using the two-way ANOVA with Bonferroni correction. j Representative images of IHC staining for Ki-67 in PDX tumors in g–i. Scale bars, 50 μm. k–m Images (k), weight (l), and volume (m) of Huh7 and PLC/PRF/5 tumor xenografts from mice fed with a -SG diet and treated with the methylated or nonmethylated peptides. Data are presented as the mean ± SD (n = 5 mice). Statistical analysis in l was performed using the two-tailed Student’s t-test, and statistical analysis in m was performed using the two-way ANOVA with Bonferroni correction. n Representative images of IHC staining for Ki-67 in Huh7 and PLC/PRF/5 tumor xenografts in k-m. Scale bars, 50 μm. Source data are provided as a Source Data file.

Back to article page