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

视黄醇脱氢酶-10 通过 TWEAK-NF-κB 轴促进人类神经胶质瘤的发展和进展

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

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.

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