KAT2A/E2F1 Promotes Cell Proliferation and Migration via Upregulating the Expression of UBE2C in Pan-Cancer

Abstract

Various studies have shown that lysine acetyltransferase 2A (<i>KAT2A</i>), E2F transcription factor 1 (<i>E2F1</i>), and ubiquitin conjugating enzyme E2 C (<i>UBE2C</i>) genes regulated the proliferation and migration of tumor cells through regulating the cell cycle. However, there is a lack of in-depth and systematic research on their mechanisms of action. This study analyzed The Cancer Genome Atlas (TCGA) to screen potential candidate genes and the regulation network of <i>KAT2A</i> and <i>E2F1</i> complex in pan-cancer. Quantitative real-time PCR (qRT-PCR) and Western blotting (WB), cell phenotype detection, immunofluorescence co-localization, chromatin immunoprecipitation assay (ChIP), and RNA-Seq techniques were used to explore the functional of a candidate gene, <i>UBE2C</i>. We found that the expression of these three genes was significantly higher in more than 10 tumor types compared to normal tissue. Moreover, <i>UBE2C</i> was mainly expressed in tumor cells, which highlighted the impacts of <i>UBE2C</i> as a specific therapeutic strategy. Moreover, <i>KAT2A</i> and <i>E2F1</i> could promote cell proliferation and the migration of cancer cells by enhancing the expression of <i>UBE2C</i>. Mechanically, <i>KAT2A</i> was found to cooperate with <i>E2F1</i> and be recruited by <i>E2F1</i> to the <i>UBE2C</i> promoter for elevating the expression of <i>UBE2C</i> by increasing the acetylation level of H3K9.