NEDD8-conjugating enzymes, E2s, include the well-studied ubiquitin-conjugating enzyme E2 M (UBE2M) and the poorly characterized ubiquitin-conjugating enzyme E2 F (UBE2F). UBE2M and UBE2F have distinct and prominent roles in catalyzing the neddylation of Cullin or non-Cullin substrates. These enzymes are overexpressed in various malignancies, conferring a worse overall survival. Targeting UBE2M to influence tumor growth by either modulating several biological responses of tumor cells (such as DNA-damage response, apoptosis, or senescence) or regulating the anti-tumor immunity holds strong therapeutic potential. Multiple inhibitors that target the interaction between UBE2M and defective cullin neddylation protein 1 (DCN1), a co-E3 for neddylation, exhibit promising anti-tumor effects. By contrast, the potential benefits of targeting UBE2F are still to be explored. It is currently reported to inhibit apoptosis and then induce cell growth; hence, targeting UBE2F serves as an effective chemo-/radiosensitizing strategy by triggering apoptosis. This review highlights the most recent advances in the roles of UBE2M and UBE2F in tumor progression, indicating these E2s as two promising anti-tumor targets.
The histone lysine methyltransferase SET (Suppressor of variegation, Enhancer
of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domaincontaining protein
(SMYD2) plays a role in the tumorigenesis of cervical squamous cell
carcinoma and endocervical adenocarcinoma (CESC). However, the prognostic
significance of SMYD2 in CESC and the link between SMYD2 and
tumor-infiltrating immune cells are unknown. The prognostic value of SMYD2
in CESC was obtained from The Cancer Genome Atlas (TCGA). SMYD2 mRNA and
protein were both highly expressed in CESC compared with normal tissues. The
high expression of SMYD2 was associated with advanced tumor status and poor
prognosis in CESC patients. SMYD2 was an independent prognostic factor for
overall survival. In vitro experiments with knockdown of SMYD2 suppressed
CESC cell migration and invasion. The online tumor immune estimation
resource (TIMER) and Kaplan-Meier analysis results revealed that the
infiltration of CD4+ T and CD8+ T cells was related to poor prognosis. In
TIMER-based multivariate Cox regression analysis, CD8+ T cells and SMYD2
were demonstrated as independent prognostic factors of CESC. In conclusion,
our data suggest that high SMYD2 expression is a predictor of poor prognosis
in CESC patients; SMYD2 could serve as a prognostic biomarker and molecular
therapeutic target for CESC.
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