Jacobs Daniel I, Qin Qin, Fu Alan, Chen Zeming, Zhou Jiangbing, Zhu Yong
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Current address: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, USA.
Oncotarget. 2018 Dec 28;9(102):37616-37626. doi: 10.18632/oncotarget.26331.
PIWI-interacting RNAs (piRNAs) are small non-coding RNAs that partner with PIWI proteins to protect germline tissues from destabilizing transposon activity. While the aberrant expression of PIWI proteins has been linked with poor outcomes for many cancers, less is known about the expression or function of piRNAs in cancer. We performed array-based piRNA expression profiling in seven pairs of normal brain and glioblastoma multiforme (GBM) tissue specimens, and identified expression of ~350 piRNAs in both tissues and a subset with dysregulated expression in GBM. Over-expression of the most down-regulated piRNA in GBM tissue, piR-8041, was found to reduce glioma cell line proliferation, induce cell cycle arrest and apoptosis, and inhibit cell survival pathways. Furthermore, pre-treatment with piR-8041 significantly reduced the volume of intracranial mouse xenograft tumors. Taken together, our study reveals reduced expression in GBM of piR-8041 and other piRNAs with tumor suppressive properties, and suggests that restoration of such piRNAs may be a potential strategy for GBM therapy.
PIWI相互作用RNA（piRNA）是一类小的非编码RNA，它们与PIWI蛋白相互作用，以保护生殖系组织免受转座子活性不稳定的影响。虽然PIWI蛋白的异常表达与许多癌症的不良预后有关，但关于piRNA在癌症中的表达或功能知之甚少。我们对七对正常脑和多形性胶质母细胞瘤（GBM）组织标本进行了基于芯片的piRNA表达谱分析，在两种组织中均鉴定出约三百五十种piRNA的表达，以及在GBM中表达失调的一个子集。在GBM组织中表达下调最明显的piRNA，即piR-8041，其过表达可减少胶质瘤细胞系的增殖，诱导细胞周期停滞和凋亡，并抑制细胞存活途径。此外，用piR-8041预处理可显著减小颅内小鼠异种移植肿瘤的体积。综上所述，我们的研究揭示了piR-8041和其他具有肿瘤抑制特性的piRNA在GBM中的表达降低，并表明恢复此类piRNA可能是GBM治疗的一种潜在策略。
