Table 1 Alterations of PHF19 expression in cancer

Glioblastoma

PHF19 expression is higher in later stages of disease and higher expression correlates with poor survival.

shRNA knockdown of PHF19L and S and rescue experiment in cell lines.

PHF19 promotes proliferation, migration, and resistance to doxorubicin through the suppression of the expression of the β-catenin ubiquitination ligase SIAH1 and the regulation of the expression of genes involved in cell cycle (CDK4, CDK6, c-MYC and Cyclin D1) and migration.

[35, 36]

Hepatocellular carcinoma

High expression of PHF19 correlates with poor survival.

MYC-driven hepatocellular carcinoma mouse model.

shRNA knockdownand PHF19 overexpression in cell lines.

Depletion of Phf19 in a MYC-driven hepatocellular carcinoma mouse model significantly decreased tumor burden and improved mouse survival.

Overexpression of PHF19S in a KRasG12D/P53KO-driven hepatocellular carcinoma mouse model significantly promoted tumorigenesis and metastasis.

PHF19 regulated the β-catenin pathway, through impairing the ubiquitination of β-catenin.

[30, 37,38,39]

Ovarian cancer

N.A.

Xenograft assay.

shRNA knockdown of PHF19L in cell lines.

shRNA mediated PHF19 KD lead to diminished cell proliferation, invasion, migration, and stemness of cell lines in vitro. In vivo xenograft assay of an ovarian cancer cell line showed that PHF19L KD significantly suppressed tumor growth.

[40, 41]

Melanoma

N.A.

siRNA knockdown of PHF19L and S in cell lines.

PHF19 promotes cell invasion and cell proliferation through upregulating the expression of Cyclin D1 and Cyclin A. contrary to what was observed in ovarian cancer cell line, PHF19 KD did not affect the expression of stemness genes (NANOG and OCT4).

[22, 42]

Gastric cancer

PHF19 is upregulated in gastric cancer tissues compared with adjacent normal stomach tissues and correlates with tumor cell differentiation state and poor outcome.

Xenograft assay.

shRNA knockdown of PHF19L in cell lines.

PHF19L promotes cell growth, colony formation and migration in vitro and tumor growth in vivo. PHF19L promotes AKT and ERK activity through regulating phosphorylation of both kinases and its overexpression increases the expression of Cyclin D1 and Cyclin E.

[43,44,45]

EWS/ETS-driven Ewing sarcoma

High levels of PHF19 expression significantly correlates with overall survival rates. The PHF19 levels in high-risk patients are significantly upregulated compared to the low-risk patients.

CRISPR-Cas9–mediated knockout of PHF19L in cell lines.

PHF19 was identified as a target for EWS/FLI1 or EWS/ERG fusions and BRD4. PHF19-KO cells result in a significant reduction in proliferation, colony forming ability, and invasive potential and showed higher sensitivity to BRD4 inhibitor JQ1.

[46]

Colorectal cancer

PHF19 is significantly overexpressed in tumors compared with normal tissues and it is high expression associate with poor overall survival, tumor progression and metastasis.

Overexpression of PHF19 in cell lines.

PHF19 overexpression mediate cell cycle progression. PHF19 overexpression led to increased protein levels of Cyclin D1, CDK4, and CDK6 and to increased percentage of cells in the S phase of the cell cycle.

[47]

Prostate cancer

see text.

see text.

see text.

see text.