Is the regulatory effect of PCAF and sirtuin 7 on phosphoglycerate kinase 1 acetylation a universal mechanism underlying hepatocellular carcinoma progression?
Authors: Changwei Dou, Xin Zheng, Qingguang Liu, Kangsheng Tu
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. TO THE EDITOR: We read the article by Hu et al.,1 in which the authors investigated the functional role of phosphoglycerate kinase 1 (PGK1) in hepatocellular carcinoma (HCC), with great interest. In this article, the authors found that the expression of PGK1 and acetylated PGK1 was increased in HCC tissues. More interestingly, this study showed that acetylation at K323 of PGK1 was critical for the oncogenic functions of PGK1 in HCC cells. Regarding K323 acetylation of PGK1, the authors demonstrated that P300/CBP‐associated factor (PCAF) could interact with PGK1 and that it promoted PGK1 acetylation in HepG2 cells. On the other hand, sirtuin 7 (SIRT7) was found to inhibit PGK1 acetylation in Huh7 cells. The authors showed that PGK1 acetylation was increased in HCC tissues and promoted cell proliferation and tumorigenesis, which suggests that PCAF promotes HCC progression while SIRT7 inhibits HCC progression, at least partly through regulating PGK1 acetylation. However, our previous study of PCAF2 and the data from the Gene Expression Omnibus database (GSE45436) (Fig. 1A) demonstrated that the PCAF level was actually decreased in HCC tissues and inhibited the growth of HCC. Moreover, another study3 and the data from Gene Expression Omnibus database (GSE45436) (Fig. 1B) showed that SIRT7 was overexpressed in HCC tissues and promoted HCC progression. Therefore, the data from other studies suggest an opposite conclusion from that of Hu et al.'s study.Figure 1: Relative expression levels of (A) PCAF and (B) SIRT7 in normal liver and HCC tissues. Data from the Gene Expression Omnibus database (GSE45436). Unpaired Student t test. **P < 0.001 versus normal liver tissues.In view of the inconsistency described above, we propose the following viewpoints which explain these inconsistent conclusions. (1) In Hu et al.'s study, the regulatory effect of PCAF and SIRT7 on PGK1 acetylation was confirmed in HepG2 and Huh7 cells. Due to the cellular heterogeneity of HCC, HepG2 and Huh7 cells may only reflect or simulate certain phenotypes of HCC cells in the human body. We question whether the regulatory effect of PCAF and SIRT7 on PGK1 acetylation is a universal phenomenon in all HCC cells or is cell type–dependent. To answer this question, it is necessary to examine this regulatory effect of PCAF and SIRT7 on PGK1 acetylation in more HCC cell lines. (2) The pathogenesis of HCC is a dynamic process. Also, HCCs at different stages or with different etiologies have different molecular mechanisms mediating their progression. Different cohorts of HCC patients from these studies have varied demographic or pathological or etiological features. This can also be a possible reason for these inconsistent conclusions in different studies. Therefore, examining the correlation between PCAF level, SIRT7 level, and PGK1 acetylation in the same cohort of HCC patients is needed.