Profiling of the small RNA populations in human testicular germ cell tumors shows global loss of piRNAs.

Tb Rounge,K Furu,Ri Skotheim,T Grotmol,E Enerly,Tb Haugen

doi:10.1186/s12943-015-0411-4

Abstract

BackgroundSmall non-coding RNAs play essential roles in gene regulation, however, the interplay between RNA groups, their expression levels and deregulations in tumorigenesis requires additional exploration. In particular, a comprehensive analysis of microRNA (miRNA), PIWI-interacting RNAs (piRNAs), and tRNA-derived small RNAs in human testis and testicular germ cell tumor (TGCT) is lacking.ResultsWe performed small RNA sequencing on 22 human TGCT samples from 5 histological subtypes, 3 carcinoma in situ, and 12 normal testis samples. miRNA was the most common group among the sequences 18–24 nt in length and showed histology-specific expression. In normal samples, most sequences 25–31 nucleotides in length displayed piRNA characteristics, whereas a large proportion of the sequences 32–36 nt length was derived from tRNAs. Expression analyses of the piRNA population demonstrated global loss in all TGCT subtypes compared to normal testis. In addition, three 5′ small tRNA fragments and 23 miRNAs showed significant (p < 10−6) differential expression in cancer vs normal samples.ConclusionsWe have documented significant changes in the small RNA populations in normal adult testicular tissue and TGCT samples. Although components of the same pathways might be involved in miRNA, piRNA and tRNA-derived small RNA biogenesis, our results showed that the response to the carcinogenic process differs between these pathways, suggesting independent regulation of their biogenesis. Overall, the small RNA deregulation in TGCT provides new insight into the small RNA interplay.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0411-4) contains supplementary material, which is available to authorized users.

Highlights

Small non-coding RNAs play essential roles in gene regulation, the interplay between RNA groups, their expression levels and deregulations in tumorigenesis requires additional exploration
In consistence with the PIWI-interacting RNA (piRNA) signature observed in previous studies [5, 16, 25], a proportion of the putative piRNA sequences in each sample group mapped to several loci in the genome
We show that the human testis is highly abundant in miRNAs, piRNAs and tRNA-derived small RNAs

Summary

Introduction

Small non-coding RNAs play essential roles in gene regulation, the interplay between RNA groups, their expression levels and deregulations in tumorigenesis requires additional exploration. Within the diverse group of ncRNA, small non-coding RNAs (sncRNAs) have emerged as potential important regulators of gene expression [3]. These RNA molecules are highly complex in terms of structural diversity and function. They are typically 19–35 nucleotides (nt) in length, interact with Argonaute family proteins [4,5,6,7], and include microRNAs (miRNAs), and PIWI-interacting RNAs (piRNAs). The miRNAs miR-371-373, miR-302 and miR-146 have previously been shown to display a TGCT-specific expression pattern [12,13,14], indicating a potential role for miRNAs in TGCT pathogenesis

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