Cell Death Differ:PGC7 promotes cancer-causing differentiation of tumors by reshaping dna methylation patterns of key developmental transcription factors

During development, lowly differentiated cancer cells usually exhibit similar esopes to their linee pregenitor cells.
in the development of normal organs are also reactivated in cancer cells, which also contributes to a large extent to the malignant transformation of tumors.
, however, the underlying molecular events are still unknown.
hepatocellular carcinoma (HCC) is one of the most common cancers with poor prognosis worldwide.
liver cancer, which retains the signal of liver preforms, is usually highly invasive and has a poor clinical prognosis.
previous studies have shown that the prognosis of HCC, which expresses bi-energy hepatocytocyte markers such as CK7 or CK19, is very poor, which also indicates that the mechanism of regulating the reversal of tumor cell linee is particularly important in the process of malignant transformation of HCC.
the study, based on an analysis of in-body hepatocellular differentiation models, the researchers found that the expression level of the parent factor PCC7 (also known as DPPA3, STELLA) was associated with liver development, HCC lineal reversal, and tumor differentiation.
PGC7 expression and liver development and liver cancer carcinogenic dedifferentiation related in the process of liver cell maturation, PGC7 expression level decreased, and from the differentiation ability of liver cells gradually differentiated to a lower degree of differentiation of liver cells.
whole genome methylation sequencing found that PGC7 can cause development-related gene initiaters to de-methylation.
network analysis based on signal paths shows that the downstream targets of PGC7 may form networks related to the activation of developmental transcription factors.
further studies have shown that the over-expression of PGC7 gives HCC cell-like characteristics.
mechanism studies have shown that PGC7 can prevent the nuclear transport of UHRF1 and promote the de-methylation of the promoters of GLI1 and MYCN, both of which are important regulatory factors for HCC self-renewal and differentiation.
PGC7/GLI1/MYCN pathrapy in HCC cancerous dedifferentiation clinical significance knock-off or inhibition of GLI1 can effectively reduce the expression of MYCN, eliminate the role of PCC7, and make HCC cells sensitive to sorafenib treatment.
, the researchers found a significant correlation between PPC7 and GLI1/MYCN and genealogical differentiation markers in clinical HCC patients.
expression of PPC7 may push HCC into a "diverged" ancestral genealogy by promoting the initiator of key developmental transcription factors to become methylated.
, the results show that HCC, which inhibits PPC7/GLI1/MYCN signaling pathlines or reversible differentiation, is inhibited and provides new treatment strategies for HCC patients.