Retinol dehydrogenase-10 promotes development and progression of human glioma via the TWEAK-NF-κB axis.

Feng Guan,Kaibin Tian,Zhuang Kang,Shuyu Hao,Junpeng Ma,Quan Zhou,Hong Chang,Zhen Wu,Junting Zhang,Hui Yin,Jian Bai,Liang Wang,Da Li,Guijun Zhang

doi:10.18632/oncotarget.22166

Abstract

Retinol dehydrogenase-10 (RDH10) is a member of the short-chain dehydrogenase/reductase family, which plays an important role in retinoic acid (RA) synthesis. Here, we show that RDH10 is highly expressed in human gliomas, and its expression correlates with tumor grade and patient survival times. In vitro, lentivirus-mediated shRNA knockdown of RDH10 suppressed glioma cell proliferation, survival, and invasiveness and cell cycle progression. In vivo, RDH10 knockdown reduced glioma growth in nude mice. Microarray analysis revealed that RDH10 silencing reduces expression of TNFRSF12A (Fn14), TNFSF12 (TWEAK), TRAF3, IKBKB (IKK-β), and BMPR2, while it increases expression of TRAF1, NFKBIA (IκBα), NFKBIE (IκBε), and TNFAIP3. This suggests that RDH10 promotes glioma cell proliferation and survival by regulating the TWEAK-NF-κB axis, and that it could potentially serve as a novel target for human glioma treatment.

Highlights

Glioma is one of the most fatal types of human brain cancers, and currently there is no effective therapy [1]
Analysis of Retinol dehydrogenase-10 (RDH10) expression from GEmini dataset[29], which integrates The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets, revealed that RDH10 levels are increased in gliomas compared with normal brain tissues, and highly increased in glioblastoma (GBM) (Figure 1B)
These results showed that the cumulative survival rate was remarkably lower in glioma patients with higher RDH10 expression than in those with lower RDH10 expression (**P < 0.01) (Table 2, Figure 1D)

Summary

Introduction

Glioma is one of the most fatal types of human brain cancers, and currently there is no effective therapy [1]. The World Health Organization (WHO) has classified human gliomas into grades I–IV [1], which are highly related to progression, treatment and prognosis. Pathological grades for glioma are usually divided into low-grade and highgrade. One of the most aggressive human brain cancers, account for 70%-80% of malignant brain tumors [2,3,4,5]. Despite achievements in surgical procedures, radiotherapy and chemotherapy, the 5-year survival rates for gliomas remain low [6, 7]. A better understanding of the responsible molecular pathways and mechanisms is urgently needed

Methods

Results

Conclusion