piRNA-8041 is downregulated in human glioblastoma and suppresses tumor growth in vitro and in vivo.
piRNA-8041 is downregulated in human glioblastoma and suppresses tumor growth in vitro and in vivo.
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DOI：
10.18632/oncotarget.26331
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发表时间：
2018-12-28
期刊：
影响因子：
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通讯作者：
Zhu, Yong
中科院分区：
文献类型：
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作者：
Jacobs, Daniel I;Qin, Qin;Zhu, Yong
PIWI相互作用rna （pirna）是一种小的非编码rna，与PIWI蛋白合作，保护种系组织免受转座子活性的破坏。虽然PIWI蛋白的异常表达与许多癌症的不良预后有关，但对pirna在癌症中的表达或功能知之甚少。我们在7对正常脑和多形性胶质母细胞瘤（GBM）组织标本中进行了基于阵列的piRNA表达谱分析，并在两种组织和GBM中发现了约350个piRNA表达异常。研究发现，在GBM组织中，过度表达最下调的piRNA piR-8041可减少胶质瘤细胞系的增殖，诱导细胞周期阻滞和凋亡，并抑制细胞存活途径。此外，用piR-8041预处理可显著减少小鼠颅内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，并提示恢复这些pirna可能是GBM治疗的潜在策略。
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.