Guan Feng, Wang Liang, Hao Shuyu, Wu Zhen, Bai Jian, Kang Zhuang, Zhou Quan, Chang Hong, Yin Hui, Li Da, Tian Kaibin, Ma Junpeng, Zhang Guijun, Zhang Junting
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Oncotarget. 2017 Oct 27;8(62):105262-105275. doi: 10.18632/oncotarget.22166. eCollection 2017 Dec 1.
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. , lentivirus-mediated shRNA knockdown of RDH10 suppressed glioma cell proliferation, survival, and invasiveness and cell cycle progression. , 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.
视黄醇脱氢酶10（RDH10）是短链脱氢酶/还原酶家族的一员，在视黄酸（RA）合成中起重要作用。在此，我们发现RDH10在人类胶质瘤中高表达，其表达与肿瘤分级和患者生存时间相关。慢病毒介导的RDH10的短发夹RNA敲低抑制了胶质瘤细胞的增殖、存活、侵袭以及细胞周期进程。RDH10敲低降低了裸鼠体内胶质瘤的生长。基因芯片分析显示，RDH10沉默降低了TNFRSF12A（Fn14）、TNFSF12（TWEAK）、TRAF3、IKBKB（IKK-β）和BMPR2的表达，而增加了TRAF1、NFKBIA（IκBα）、NFKBIE（IκBε）和TNFAIP3的表达。这表明RDH10通过调节TWEAK-NF-κB轴促进胶质瘤细胞的增殖和存活，并且它可能潜在地成为人类胶质瘤治疗的新靶点。
