LncRNA HSP90AA1-IT1 promotes gliomas by targeting miR-885-5p-CDK2 pathway.
LncRNA HSP90AA1-IT1 promotes gliomas by targeting miR-885-5p-CDK2 pathway.
复制标题
LncRNA HSP90AA1-IT1 通过靶向 miR-8855p-CDK2 通路促进神经胶质瘤
DOI：
10.18632/oncotarget.20777
复制
发表时间：
2017-09-26
期刊：
影响因子：
--
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Gao T;Gu G;Tian J;Zhang R;Zheng X;Wang Y;Pang Q;Liu Q
众所周知，ncrna在各种类型的癌症中都是重要的调节因子，然而，它们在癌症中的功能和贡献仍然没有得到充分的定义。在本研究中，我们报道了一种名为HSP90AA1- it1 （HSP90AA1子转录本1）的长链非编码RNA （lncRNA）的表达水平似乎与胶质瘤的病理分级相关，高水平的HSP90AA1- it1提示预后不良。在胶质瘤细胞系中，下调HSP90AA1-IT1可显著抑制细胞活力、增殖、EMT、侵袭和迁移，并增加细胞凋亡和异常细胞周期进程。这些细胞在体内的致瘤能力也被抑制。我们进一步证明HSP90AA1-IT1的致癌作用可以通过直接结合miR-885-5p介导。HSP90AA1-IT1与胶质瘤发生的关键调节因子CDK2具有相同的结合位点，与miR-885-5p竞争性结合，从而阻止CDK2抑制miR-885-5p介导的转录后抑制。综上所述，我们认为HSP90AA1-IT1通过miR-885-5p-CDK2信号轴调控胶质瘤的发展来发挥其功能，这为其在肿瘤发生中的作用提供了新的视角，从而为胶质瘤的治疗提供了潜在的治疗靶点。
It is well established that ncRNAs are emerging as important regulators in various types of cancers, however, their functions and contributions in cancers remain insufficiently defined. In this study, we reported the expression levels of a long noncoding RNA (lncRNA), named HSP90AA1-IT1 (HSP90AA1 intronic transcript 1), appeared to correlate with the pathological grades of gliomas and high level of HSP90AA1-IT1 indicated poor prognosis. Downregulation of HSP90AA1-IT1 in the glioma cell lines significantly suppressed cell viability, proliferation, EMT, invasion and migration in addition to an increase in apoptosis and aberrant cell cycle progression. The tumorigenic capacity of these cells in vivo were also inhibited. We further demonstrated that the oncogenic effects of HSP90AA1-IT1 could be mediated by a direct binding to miR-885-5p. Sharing the same binding sites with CDK2, a key regulator in gliomagenesis, HSP90AA1-IT1 competitively bound to miR-885-5p, thereby prevented CDK2 from miR-885-5p mediated post-transcriptional repression. Taken together, it is concluded that HSP90AA1-IT1, performs its function via regulating the development of gliomas through miR-885-5p-CDK2 signaling axis, and this has added new perspective to its role in tumorigenesis, thus providing potential therapeutic targets for glioma treatment.