piRNA-8041 is downregulated in human glioblastoma and suppresses tumor growth in vitro and in vivo
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Daniel I. Jacobs1, Qin Qin1,2, Alan Fu1,3, Zeming Chen4, Jiangbing Zhou4,5 and Yong Zhu1
1Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA
2Current address: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, USA
3Current Address: Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA
4Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA
5Department of Biomedical Engineering, Yale University, New Haven, CT, USA
Yong Zhu, email: firstname.lastname@example.org
Keywords: piRNA, PIWI-interacting RNA, glioma, GBM
Received: November 24, 2016 Accepted: September 13, 2017 Published: December 28, 2018
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.
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