Chen Zhixu, Liu Zezheng, Yang Yang, Zhu Zhaoyin, Liang Ridong, Huang Bin, Wu Di, Yang Lei, Lu Hai, Jin Dadi, Li Qingchu
Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182, China.
Oncotarget. 2018 Jan 13;9(42):26770-26786. doi: 10.18632/oncotarget.24247. eCollection 2018 Jun 1.
Long non-coding RNAs (lncRNAs) have been shown to exert essential roles in development and progression of tumors. Here we discovered a novel lncRNA, RAB11B antisense RNA (RAB11B-AS1), which is markedly down-regulated in human osteosarcoma (OS) and associated with OS metastasis and poor prognosis. We find that reduction of RAB11B-AS1 significantly facilitates proliferation, migration and invasiveness and prevents apoptosis of OS cells and results in lower sensitivity to cisplatin in these cells. In contrast, up-regulation of RAB11B-AS1 suppresses the aggressive behaviors of OS cells. Mechanistically, down-regulation of RAB11B-AS1 elevates its sense-cognate gene RAB11B expression at both mRNA and protein levels. RAB11B-AS1 expression correlates negatively with RAB11B expression in OS tissues. Luciferase reporter assay illuminated that RAB11B-AS1 regulates RAB11B expression through antisense pairing. Most importantly, all the effects of RAB11B-AS1 were abrogated by RAB11B down-regulation. Thus our findings revealed that lnc-RAB11B-AS1 prevents osteosarcoma development and progression via inhibiting RAB11B expression, indicating lnc-RAB11B-AS1 as a potential therapeutic target for osteosarcoma.
长链非编码RNA(lncRNAs)已被证明在肿瘤的发生发展过程中发挥重要作用。在此,我们发现了一种新型lncRNA,即RAB11B反义RNA(RAB11B-AS1),它在人类骨肉瘤(OS)中显著下调,且与OS转移及不良预后相关。我们发现,RAB11B-AS1的减少显著促进了OS细胞的增殖、迁移和侵袭能力,并抑制了其凋亡,导致这些细胞对顺铂的敏感性降低。相反,RAB11B-AS1的上调则抑制了OS细胞的侵袭性行为。机制上,RAB11B-AS1的下调在mRNA和蛋白质水平上均提高了其正义同源基因RAB11B的表达。在OS组织中,RAB11B-AS1的表达与RAB11B的表达呈负相关。荧光素酶报告基因检测表明,RAB11B-AS1通过反义配对调节RAB11B的表达。最重要的是,RAB11B的下调消除了RAB11B-AS1的所有作用。因此,我们的研究结果表明,lnc-RAB11B-AS1通过抑制RAB11B的表达来阻止骨肉瘤的发生和发展,这表明lnc-RAB11B-AS1可能是骨肉瘤的一个潜在治疗靶点。