Abstract
Human PIWI-interacting RNAs (piRNAs) are known to be expressed in germline cells, functionally silencing LINEs and SINEs. Their expression patterns in somatic tissues are largely uncharted. We analyzed 6,260 human piRNA transcriptomes derived from non-malignant and tumour tissues from 11 organs. We discovered that only 273 of the 20,831 known piRNAs are expressed in somatic non-malignant tissues. However, expression patterns of these piRNAs were able to distinguish tissue-of-origin. A total of 522 piRNAs are expressed in corresponding tumour tissues, largely distinguishing tumour from non-malignant tissues in a cancer-type specific manner. Most expressed piRNAs mapped to known transcripts, contrary to “piRNA clusters” reported in germline cells. We showed that piRNA expression can delineate clinical features, such as histological subgroups, disease stages, and survival. PiRNAs common to many cancer types might represent a core gene-set that facilitates cancer growth, while piRNAs unique to individual cancer types likely contribute to cancer-specific biology.
Highlights
Human P-element–induced wimpy testis (PIWI)-interacting RNAs are known to be expressed in germline cells, functionally silencing LINEs and SINEs
PiRNA expression has been primarily described in germline tissues, the first goal of this study was to systematically assess PIWI-interacting RNAs (piRNAs) transcriptome patterns across human somatic tissues (Table 1)
We evaluated the expression of 20,831 unique piRNAs in normal tissues (n = 5 08) derived from 10 different anatomical sites: bladder, breast, colon, head and neck, kidney, lung, prostate, stomach, thyroid, and uterine corpus available from The Cancer Genome Atlas (TCGA) consortium
Summary
Human PIWI-interacting RNAs (piRNAs) are known to be expressed in germline cells, functionally silencing LINEs and SINEs. Based largely on differences in biogenesis and structure, small RNAs can be broadly divided into three groups: small interfering RNAs (siRNAs), microRNAs (miRNAs) and PIWI-interacting RNA (piRNAs) These interact with either the AGO (siRNAs, miRNAs) or PIWI subfamily (piRNAs) to form gene regulatory RNA/protein complexes[2,3]. PiRNAs are small (24–32 nucleotides), single-stranded non-coding RNAs, that have highly conserved functions across species, such as transposon silencing and stem cell maintenance in germline tissues[6,10,11,12]. Some components of the PIWI biogenesis machinery have been characterized[24,37]; but tumour specific expression of piRNAs are limited to either single gene studies[38,39], or expression profiles of a few representative tumours[40,41,42] or cell lines[42,43,44,45] for a few types of cancers
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