Abstract: Ubiquitin-like with PHD and Ring finger domains 1 (UHRF1) is an epigenetic regulator that maintains DNA methylation modification and plays critical roles in embryonic development, tumor progress and prognosis. In this study, the differential expression genes regulated by UHRF1 was identified, and the associated cell functions, metabolic pathways, and related diseases these genes involved were investigated. Total RNA extracted from UHRF1 knockdown cells (MCF-7/shRNA-UHRF1) or scramble cells (MCF-7/shRNA-Scramble) as a control was subjected to RNA-Seq analysis, then the differential expression genes were screened by using DESeq2 software and partially validated by qRT-PCR. Gene ontology (GO), Kyoto Encylopedia of Genes and Genomes (KEGG) and Disease ontology (DO) analyses were employed to investigate the potential biological functions of these genes. The results showed that a total of 2926 genes expression were regulated by UHRF1. Among them, 1453 genes were down-regulated and 1473 genes were up-regulated by UHRF1 knockdown. GO and KEGG analysis showed that these genes were primarily enriched in cell metabolism, immune regulation, signal transduction, cardiovascular disease and tumorigenesis. DO analysis showed that they were mainly involved in cancer and neurological diseases. These results suggested that DNA methylation mediated by the epigenetic regulatory factor UHRF1 can regulate the differential expression of genes at the transcriptional level, providing data support for the participation of UHRF1 in the regulation of relevant signaling pathways.

Key words: UHRF1, MCF-7 cell, epigenetic regulator, RNA-Seq, differentially expressed genes