Liu Liyun, Zheng Mingxia, Wang Xinwei, Gao Yanzheng, Gu Qingguo
Henan Provincial People's Hospital, School of Clinical Medicine, Henan University, Zhengzhou, China.
Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, Zhengzhou, China.
Front Pharmacol. 2020 May 15;11:641. doi: 10.3389/fphar.2020.00641. eCollection 2020.
Long non-coding RNAs (lncRNAs) are emerging as important regulators of the processes involved in cancer development and progression. The molecular mechanism by which lncRNAs regulate the progression of osteosarcoma has not been clearly elucidated. The role of NR_136400, which is an uncharacterized lncRNA, has not been previously reported in osteosarcoma (OS). In the present study, we demonstrated that NR_136400 was downregulated in OS cells and that its downregulation promoted OS cell proliferation, apoptosis, and invasion. NR_136400 downregulation facilitated EMT by inhibiting the expression of E-cadherin and elevating the expression of ZEB1, Snail, and fibronectin. experiments using a xenograft tumor mouse model revealed that NR_136400 downregulation promoted tumor growth in OS. Mechanistic investigations demonstrated that NR_136400 competitively bound to miR-8081 and then upregulated the protein expression of TUSC5. Taken together, a newly identified regulatory mechanism of the lncRNA NR_136400/miR-8081/TUSC5 axis was systematically studied in OS, providing a promising target for therapeutic treatment.
长链非编码RNA（lncRNAs）正逐渐成为癌症发生和发展过程中的重要调节因子。lncRNAs调节骨肉瘤进展的分子机制尚未完全阐明。NR_136400是一种未被表征的lncRNA，其在骨肉瘤（OS）中的作用此前尚未见报道。在本研究中，我们证明NR_136400在OS细胞中表达下调，其下调促进了OS细胞的增殖、凋亡和侵袭。NR_136400的下调通过抑制E-钙黏蛋白的表达并提高ZEB1、Snail和纤连蛋白的表达促进了上皮-间质转化（EMT）。使用异种移植肿瘤小鼠模型的实验表明，NR_136400的下调促进了OS中的肿瘤生长。机制研究表明，NR_136400与miR-8081竞争性结合，进而上调TUSC5的蛋白表达。综上所述，我们在OS中系统地研究了新发现的lncRNA NR_136400/miR-8081/TUSC5轴调控机制，为治疗提供了一个有前景的靶点。
