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 (KAT2A), E2F transcription factor 1 (E2F1), and ubiquitin conjugating enzyme E2 C (UBE2C) 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 KAT2A and E2F1 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, UBE2C. We found that the expression of these three genes was significantly higher in more than 10 tumor types compared to normal tissue. Moreover, UBE2C was mainly expressed in tumor cells, which highlighted the impacts of UBE2C as a specific therapeutic strategy. Moreover, KAT2A and E2F1 could promote cell proliferation and the migration of cancer cells by enhancing the expression of UBE2C. Mechanically, KAT2A was found to cooperate with E2F1 and be recruited by E2F1 to the UBE2C promoter for elevating the expression of UBE2C by increasing the acetylation level of H3K9.

TUBB, a robust biomarker with satisfying abilities in diagnosis, prognosis, and immune regulation via a comprehensive pan-cancer analysis

“…E2F1 has been reckoned as a tumor-promoting gene. From one pan-cancer analysis, the KAT2A/E2F1 complex promotes cell proliferation and metastasis by upregulating the UBE2C expression ( Lin et al, 2022 ). An in SARC, the role of E2F1 has already been widely explored.…”

The histone modifier KAT2A presents a selective target in a subset of well-differentiated microsatellite-stable colorectal cancers

“…Both HAT inhibitors as well as HDAC inhibitors have been suggested as potent therapeutic options in preclinical models and clinical trials for various cancers, including CRC (49). Furthermore, it has been demonstrated that KAT2A expression is elevated in CRC, and the knockdown of KAT2A has been shown to reduce the proliferation and migration of CRC cell lines (11,50).…”

Bromodomain (BrD) Family Members as Regulators of Cancer Stemness—A Comprehensive Review

“…Specifically, KAT2A upregulation associates with worse patient outcomes in several cancers, including breast, lung, colon, and renal cancers [ 55 , 56 , 57 , 58 ]. KAT2A contributes to cancer through the control of transcriptional activity, mainly the co-activation of E2F and Myc transcriptional targets [ 59 ]. In renal cancer, KAT2A promotes tumor growth and accelerates the metastatic phenotype of cancer cells by regulating glycolytic metabolism through MCT1 upregulation [ 60 ].…”