Abstract

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.

Highlights

  • PIWI-interacting RNAs are small noncoding RNAs with highly conserved functions in the protection of germline stem cells from transposable element mobilization [1, 2]

  • Its significance outside of this context remains largely enigmatic, and no previous studies have examined the role of PIWI-interacting RNAs (piRNAs) in many cancer types, including glioma

  • Our array-based piRNA expression profiling results indicated that ~350 piRNAs are expressed in both normal and glioblastoma multiforme (GBM) brain tissue

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Summary

Introduction

PIWI-interacting RNAs (piRNAs) are small (mostly 26-32 nt) noncoding RNAs with highly conserved functions in the protection of germline stem cells from transposable element mobilization [1, 2]. PIWIpiRNA ribonucleoprotein complexes recruit chromatinremodeling machinery to complementary transposable element targets, where heritable epigenetic modifications are established (via DNA methylation in mammals) [8,9,10]; we and others have shown that this may occur at protein-coding genes [11,12,13]. Recent studies have suggested that piRNAs may act post-transcriptionally in mRNA silencing [6, 7, 14, 15]. A recent comprehensive analysis of piRNA expression outside of the germline utilizing www.oncotarget.com

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