In Vitro Biological Characterization of DCUN1D5 in DNA Damage Response

Abstract

Background: Novel prognostic biomarkers or therapeutic molecular targets for laryngeal squamous cell carcinoma (LSCC) are an urgent priority. We here sought to identify multiple novel LSCC-associated genes. Methods: Using high-density microarray expression profiling, we identified multiple genes that were significantly altered between human LSCCs and paired normal tissues. Potential oncogenic functions of one such gene, DCUN1D5, were further characterized in vitro. Results: Our results demonstrated that DCUN1D5 was highly expressed in LSCCs. Overexpression of DCUN1D5 in vitro resulted in 2.7-fold increased cellular migration, 67.5% increased invasive capacity, and 2.6-fold increased proliferation. Endogenous DCUN1D5 expression was decreased in a time-dependent manner after genotoxic stress, and silencing of DCUN1D5 by siRNA decreased the number of cells in the S phase by 10.2% and increased apoptosis by 11.7%. Conclusion: Our data suggest that DCUN1D5 in vitro might have vital roles in DNA damage response, but further studies are warranted to assess its significance in vivo.

Oncogenic Function of SCCRO5/DCUN1D5 Requires Its Neddylation E3 Activity and Nuclear Localization

“…It is well established that overexpression of SCCRO promotes its function as an oncogene (16, 18). By showing that overexpression of SCCRO5 has transforming activity and by associating it with an aggressive clinical course in human cancers, our data support the position that SCCRO5 may function as an oncogene as well (20). Its role in cancer pathogenesis is further validated by our findings, which indicate the presence of an oncogene addiction phenotype in cancer cell lines that have high endogenous levels of SCCRO5 expression.…”

“…Since SCCRO5 promotes neddylation of all cullins (with the possible exception of Cul4A), it putatively can regulate the ubiquitination of a myriad of proteins, resulting in diverse cellular effects (42). Guo and colleagues suggest that SCCRO5 may be involved in regulating ubiquitination of the proteins involved in DNA-damage repair (20). Consistent with this suggestion, SCCRO5 was found to be part of a panel of seven genes whose expression score predicts radiation response in patients with cervical cancer (47).…”

“…SCCRO3 has also been shown to play a role in oncogenesis (19). Recent work indicates that SCCRO5 has oncogenic activity (20). However, the precise mechanisms by which the NLS-containing SCCRO paralogues promote oncogenesis remain unknown.…”

“…Fine-mapping of 11q22.2-q22.3 in cervical, oral, and lung cancers has shown that SCCRO5 ( MGC2714 ) is located within the minimal common region of amplification (27, 30, 32). SCCRO5 is upregulated in laryngeal SCC and putatively plays a role in its pathogenesis (20). Given the established role of SCCRO in oncogenesis, we questioned whether SCCRO5 drives selection for 11q22 amplification in human cancers and sought to elucidate the mechanisms involved.…”

Antiproliferative Effects of Celecoxib in Hep-2 Cells through Telomerase Inhibition and Induction of Apoptosis

“…Chemotherapy or chemotherapy combined radiotherapy could improve the overall survival and organ retention for recurrence of advanced laryngeal cancer patients (Gino et al, 2006). Squamous cell carcinoma accounts for 90% of all malignancies of the larynx and chromosomal aberrations accumulate can result in a more aggressive cancer phenotype as disease stage advance (Guo et al, 2012).…”