The epigenetic factor UHRF1 regulates transcription by modulating DNA methylation and histone modification, and plays critical roles in proliferation, development, and tumorigenesis.
However, whether the overexpressed UHRF1 contributes to the establishment and maintenance of tumor methylomes and whether this process can affect the tumorigenesis remain unclear.
Compelling evidence suggests a strong link between UHRF1 overexpression and tumorigenesis, substantiating its ability to act as a potential biomarker for cancer diagnosis and prognosis.
Several in vitro and in vivo works have reported the direct implication of the epigenetic player UHRF1 in tumorigenesis through the repression of TSGs expression and suggested UHRF1 as a promising target for cancer treatment.
The UHRF1 protein is pivotal for DNA methylation and heterochromatin formation, leading to decreased expressions of tumor suppressor genes and contributing to tumorigenesis.
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1), as an epigenetic regulator, plays important roles in the tumorigenesis and cancer progression.
We propose that UHRF1 overexpression is a mechanism underlying DNA hypomethylation in cancer cells and that senescence is a primary means of restricting tumorigenesis due to epigenetic disruption.
Thus, our data revealed that the global DNA hypomethylation induced by the DNMT1/PCNA/UHRF1 disruption is an oncogenic event of human tumorigenesis, an inducer of epigenetic and genetic signatures frequently observed in several human cancers, and is an initiator of oncogenic events.
These findings demonstrate that UHRF1 is a critical negative regulator of TIP60 and suggest that UHRF1-mediated effects on p53 may contribute, at least in part, to its role in tumorigenesis.
Ubiquitin-like with PHD and ring-finger domain 1 (UHRF1) binds to methylated promoters of a number of tumor-suppressor genes, including p16INK4A and p14ARF, by forming complexes with DNA methyltransferases and HDAC1, resulting in the induction of carcinogenesis.
It is reported that UHRF1 is obviously upregulated in various human malignancies, but unchanged in differentiated tissues, suggesting that UHRF1 plays a crucial role in carcinogenesis and can be a useful anticancer drug target.
Recently, it was revealed that UHRF1 plays important roles not only in carcinogenesis, but also in toxoplasmosis, which is occasionally fatal to people with a weakened immune system, and can cause blindness in the major pathology of ocular toxoplasmosis.