Gao Taihong, Gu Guangyan, Tian Jingxia, Zhang Rui, Zheng Xiangrong, Wang Yanan, Pang Qi, Liu Qian
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China.
Department of Histology and Embryology, Shandong University School of Medicine, Jinan 250012, Shandong, China.
Oncotarget. 2017 Sep 8;8(43):75284-75297. doi: 10.18632/oncotarget.20777. eCollection 2017 Sep 26.
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 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.
众所周知，非编码RNA（ncRNAs）正在成为各类癌症中的重要调节因子，然而，它们在癌症中的功能和作用仍未得到充分界定。在本研究中，我们报告了一种名为HSP90AA1-IT1（HSP90AA1内含子转录本1）的长链非编码RNA（lncRNA）的表达水平，其似乎与胶质瘤的病理分级相关，且HSP90AA1-IT1的高水平预示着预后不良。在胶质瘤细胞系中下调HSP90AA1-IT1除了会增加细胞凋亡和异常细胞周期进程外，还能显著抑制细胞活力、增殖、上皮-间质转化（EMT）、侵袭和迁移。这些细胞的致瘤能力也受到抑制。我们进一步证明，HSP90AA1-IT1的致癌作用可通过与miR-885-5p直接结合来介导。HSP90AA1-IT1与胶质瘤发生中的关键调节因子CDK2共享相同的结合位点，竞争性地与miR-885-5p结合，从而阻止CDK2受到miR-885-5p介导的转录后抑制。综上所述，得出结论：HSP90AA1-IT1通过miR-885-5p-CDK2信号轴调节胶质瘤的发展来发挥其功能，这为其在肿瘤发生中的作用增添了新的视角，从而为胶质瘤治疗提供了潜在的治疗靶点。
