UBE2C Is a Transcriptional Target of the Cell Cycle Regulator FOXM1

Abstract

FOXM1 (forkhead box protein M1) is a transcription factor that participates in all stages of tumor development, mainly through the control of cell cycle and proliferation, regulating the expression of genes involved in G1/S and G2/M transition and M phase progression. The ubiquitin conjugating enzyme E2 (UBE2C) is a member of the anaphase promoting complex/cyclosome, promoting the degradation of several target proteins along cell cycle progression, during metaphase/anaphase transition. FOXM1 and UBE2C have been found overexpressed in a wide range of different solid tumors. Therefore, the aim of this study was to investigate whether UBE2C is a transcriptional target of FOXM1, using esophageal squamous cell carcinoma (ESCC) as a model, in addition to several cancer-deposited data. Our results show that FOXM1 and UBE2C expression present a positive correlation in normal tissues and in 25 distinct tumor types, including ESCC, where these genes are overexpressed. Moreover, FOXM1 binds to UBE2C promoter region in ESCC cell line and transcriptionally activates it, leading to UBE2C upregulation. In conclusion, this study provides evidences that FOXM1 transcriptionally regulates UBE2C expression in ESCC and their deregulation may be a general phenomenon in human neoplasias.

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“…Western blot analyses were performed as previously described 66 . The primary antibodies used were: anti-Cebpd #7077 (ProSci, Poway, CA, USA); anti-Fos sc-166940 (Santa Cruz Biotechnology, Dallas, TX, USA); anti-Bcl2l1 #2762 (Cell Signaling, Danvers, MA, USA).…”

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“…In addition, we found that UBE2C mRNA expression levels were high in certain triple negative cell lines. Nicolau-Neto et al reported that UBE2C is a transcriptional target of the cell cycle regulator FOXM1, which was identified as a specific marker for TNBC (35,36).…”

Integrated Analysis of Hub Genes and Pathways In Esophageal Carcinoma Based on NCBI’s Gene Expression Omnibus (GEO) Database: A Bioinformatics Analysis

“…Meanwhile, the expression of UBE2C, TTK, and TPX2 is involved in ESCA pathology and prognosis. As a ubiquitin-conjugating enzyme, UBE2C promotes the degradation of several cell cycle-regulated proteins that control progression through mitosis [ 55 ]. Knockdown of UBE2C significantly inhibits cell proliferation via cell-cycle regulation, in in-vitro ESCA cell models, particularly in TE-1 cell lines [ 56 ].…”