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

Juhyun Shin; Jun-Ha Choi; Seunghwa Jung; Somi Jeong; Jeongheon Oh; Do-Young Yoon; Man Hee Rhee; Jaehong Ahn; Se-Hyuk Kim; Jae-Wook Oh

doi:10.3389/fgene.2019.00884

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

Front Genet. 2019 Sep 19:10:884. doi: 10.3389/fgene.2019.00884. eCollection 2019.

Authors

Juhyun Shin^{1

2}, Jun-Ha Choi², Seunghwa Jung², Somi Jeong², Jeongheon Oh², Do-Young Yoon³, Man Hee Rhee⁴, Jaehong Ahn⁵, Se-Hyuk Kim⁶, Jae-Wook Oh^{1

2}

Affiliations

¹ Animal Resources Research Center, Konkuk University, Seoul, South Korea.
² Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, South Korea.
³ Department of Bioscience and Biotechnology, Konkuk Institute of Technology, Konkuk University, Seoul, South Korea.
⁴ Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, South Korea.
⁵ Department of Ophthalmology, Ajou University School of Medicine, Suwon, South Korea.
⁶ Department of Neurosurgery, Ajou University School of Medicine, Suwon, South Korea.

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.

Keywords: Mu-2-related death-inducing gene; cancer cell apoptosis; gene expression omnibus; glioblastoma multiforme; patient survival; the cancer genome atlas.