MUDENG Expression Profiling in Cohorts and Brain Tumor Biospecimens to Evaluate Its Role in Cancer

Abstract

Mu-2-related death-inducing gene (MUDENG, MuD) has been reported to be involved in the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-associated apoptotic pathway of glioblastoma multiforme (GBM) cells; however, its expression level, interactors, and role in tumors are yet to be discovered. To investigate whether MuD expression correlates with cancer progression, we analyzed The Cancer Genome Atlas (TCGA) database using UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA). Differential expression of MuD was detected in 6 and 10 cancer types, respectively. Validation performed using data from the Gene Expression Omnibus database showed that MuD expression is downregulated in KIRC tumor and correlate with higher chance of survival. Upregulation of MuD expression in GBM tumors was detected through GEPIA and high MuD expression correlated with higher survival in proneural GBM, whereas the opposite was observed in classical GBM subtype. GBM biospecimens analysis shows that MuD protein level was upregulated in three of six specimens, whereas mRNA level remained relatively unaltered. Therefore, MuD may exert differential effects according to subtypes, and/or be subjected to post-translational regulation in GBM. Correlation analysis between GBM cohort database and experiments using GBM cell lines revealed its positive effect on regulation of protein phosphatase 2 regulatory subunit B’Epsilon (PPP2R5E) and son of sevenless homolog 2 (SOS2). STRING database analysis indicated that the components of adaptor protein complexes putatively interacted with MuD but showed no correlation in terms of survival of patients with different GBM subtypes. In summary, we analyzed the expression of MuD in publicly available cancer patient data sets, GBM cell lines, and biospecimens to demonstrate its potential role as a biomarker for cancer prognosis and identified its candidate interacting molecules.

Cinnamaldehyde-Rich Cinnamon Extract Induces Cell Death in Colon Cancer Cell Lines HCT 116 and HT-29

“…Western blot analysis showed that CRCE treatment resulted in PARP cleavage in these cells in a dose-dependent manner. The mu-2-related, death-inducing gene (MUDENG, MuD) was reported to be involved in the apoptotic pathway in various cancer cell lines [48][49][50]. Subsequent studies demonstrated the cleavage of MUDENG by active caspase-3 during TRAIL-induced apoptotic signaling [51] and the subsequent activation of the anti-apoptotic function of MUDENG near the BH3-interacting domain death agonist (Bid) and B-cell lymphoma 2 (Bcl-2) junction [26].…”

SOS2 Comes to the Fore: Differential Functionalities in Physiology and Pathology

“…In this regard, direct exome sequencing has detected the presence of missense-activating mutations in SOS2 in a small percentage of gallbladder carcinomas [ 65 ], and also in a subtype of desmoplastic melanomas [ 66 ]. Recent analysis of gene expression profiles has also reported MuD-dependent upregulation of SOS2 expression in cohorts of TCGA glioblastomas (GBM), and a correlation between high expression of the two genes and longer survival of proneural GBM patients [ 67 ]. Finally, a whole-exome sequencing analysis carried out on non-small cell lung cancer samples demonstrated a direct correlation between SOS2 and resistance mechanisms to Osimertinib [ 38 ].…”