UHRF1 promotes breast cancer progression by suppressing KLF17 expression by hypermethylating its promoter.

UHRF1 is an epigenetic regulator and perform pivotal functions in cell tumorigenesis. We found UHRF1 is increased in breast cancer and patients with high UHRF1 levels have poorer prognoses than those with low UHRF1 levels. However, the underlying mechanisms remain largely unknown. Here, we found overexpression UHRF1 indeed promoted cell proliferation and migration, whereas its downregulation had the opposite functions. , UHRF1 also accelerated tumor growth. Mechanistically, microarrays were performed in MDA-MB-231 sh-UHRF1 and NC cells and KLF17, with rich CpG islands on its promoter region, finally caused our attention. Then, the expression of UHRF1 and KLF17 was testified negatively correlated in breast cancer cell lines and tissues. Additionally, the inhibition of cell proliferation and migration by UHRF1 depletion can be rescued by KLF17 silencing, suggesting KLF17 is downstream gene of UHRF1. The potential mechanism is that overexpression UHRF1 increased methylation of CpG nucleotides on KLF17 promoter, while UHRF1 silence decreased methylation. Collectively, our results demonstrated that increased UHRF1 can promote breast cancer cell proliferation and migration via silencing of KLF17 expression through CpG island methylation on its promoter.