Project description:There is mounting evidence indicating that piRNAs are also present in somatic cells where they may accomplish additional regulatory tasks. The aim of this study was to identify the piRNAs expressed in pancreatic islets and to determine whether they are involved in the control of beta-cell activities. piRNA profiling of rat pancreatic islets was performed by microarray. We detected about 18’000 piRNAs in rat pancreatic islets, many of which were differentially expressed throughout islet postnatal development.
Project description:There is mounting evidence indicating that piRNAs are also present in somatic cells where they may accomplish additional regulatory tasks. The aim of this study was to identify the piRNAs expressed in pancreatic islets and to determine whether they are involved in the control of beta-cell activities. piRNA profiling of rat pancreatic islets was performed by microarray. We detected about 18’000 piRNAs in rat pancreatic islets, many of which were differentially expressed throughout islet of Goto-Kakizaki rats, a well-established model of Type 2 diabetes.
Project description:PIWI proteins and their bound PIWI-interacting RNAs (piRNAs) are found in animal germlines and are essential for fertility, but their functions outside of the gonad are not well understood. The cnidarian Hydra is a simple metazoan with well-characterized stem/progenitor cells that provides a unique model for analysis of PIWI function. Here we report that Hydra has two PIWI proteins, Hydra PIWI (Hywi) and Hydra PIWI-like (Hyli), both of which are expressed in all Hydra stem/progenitor cells, but not in terminally differentiated cells. We identified ∼15 million piRNAs associated with Hywi and/or Hyli and found that they exhibit the ping-pong signature of piRNA biogenesis. Hydra PIWI proteins are strictly cytoplasmic and thus likely act as posttranscriptional regulators. To explore this function, we generated a Hydra transcriptome for piRNA mapping. piRNAs map to transposons with a 25- to 35-fold enrichment compared with the abundance of transposon transcripts. By sequencing the small RNAs specific to the interstitial, ectodermal, and endodermal lineages, we found that the targeting of transposons appears to be largely restricted to the interstitial lineage. We also identified putative nontransposon targets of the pathway unique to each lineage. Finally we demonstrate that hywi function is essential in the somatic epithelial lineages. This comprehensive analysis of the PIWI-piRNA pathway in the somatic stem/progenitor cells of a nonbilaterian animal suggests that this pathway originated with broader stem cell functionality.
Project description:Piwi-interacting RNAs (piRNAs), whose role in germline maintenance has been established, are now also being classified as post-transcriptional regulators of gene expression in somatic cells. PIWI proteins, central to piRNA biogenesis, have been identified as genetic and epigenetic regulators of gene expression. piRNAs/PIWIs have emerged as potential biomarkers for cancer but their relevance to breast cancer has not been comprehensively studied. piRNAs and mRNAs were profiled from normal and breast tumor tissues using next generation sequencing and Agilent platforms, respectively. Gene targets for differentially expressed piRNAs were identified from mRNA expression dataset. piRNAs and PIWI genes were independently assessed for their prognostic significance (outcomes: Overall Survival, OS and Recurrence Free Survival, RFS). We discovered eight piRNAs as novel independent prognostic markers and their association with OS was confirmed in an external dataset (The Cancer Genome Atlas). Further, PIWIL3 and PIWIL4 genes showed prognostic relevance. 306 gene targets exhibited reciprocal relationship with piRNA expression. Cancer cell pathways such as apoptosis and cell signaling were the key Gene Ontology terms associated with the regulated gene targets. Overall, we have captured the entire cascade of events in a dysregulated piRNA pathway and have identified novel markers for breast cancer prognostication.
Project description:PIWI-interacting RNAs (piRNAs) are a less-studied class of small non-coding RNAs approximately 24-31 nucleotides in length. They express in germline and somatic cells and form complexes with PIWI proteins to exert regulatory effects. New studies show that piRNAs are aberrantly expressed in various cancers. In this review, we focus on those piRNAs that are associated with cancer hallmarks such as proliferation, invasion, and chemoresistance and discuss their potential as biomarkers for cancer diagnosis and prognosis.
Project description: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 and glioblastoma multiforme (GBM) tissue specimens and identified expression of ~350 piRNAs in both tissues and a subset with dysregulated expression in GBM. Several down-regulated piRNAs inhibited proliferation when transfected into glioma cell lines while those equivalently expressed in tumor and normal tissues did not, consistent with piRNA-specific tumor-suppressive roles. Upregulation of the most underexpressed piRNA, piR-8041, was found to induce cell cycle arrest and apoptosis and to alter transcriptional levels of several genes involved in stress and cell survival pathways. Additionally, the volume of intracranial mouse xenograft tumors was significantly reduced for approximately ten days after pre-implantation transfection with piR-8041. Taken together, our study reveals a previously unidentified functional role for piRNAs as tumor suppressors in gliomagenesis, and suggests that restoration of piRNA levels may be a potential strategy for GBM therapy.
Project description:PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that bind PIWI family proteins exclusively expressed in the germ cells of mammalian gonads. MIWI2-associated piRNAs are essential for silencing transposons during primordial germ cell development, and MIWI-bound piRNAs are required for normal spermatogenesis during adulthood in mice. Although piRNAs have long been regarded as germ cell-specific, increasing lines of evidence suggest that somatic cells also express piRNA-like RNAs (pilRNAs). Here, we report the detection of abundant pilRNAs in somatic cells, which are similar to MIWI-associated piRNAs mainly expressed in pachytene spermatocytes and round spermatids in the testis. Based on small RNA deep sequencing and quantitative PCR analyses, pilRNA expression is dynamic and displays tissue specificity. Although pilRNAs are similar to pachytene piRNAs in both size and genomic origins, they have a distinct ping-pong signature. Furthermore, pilRNA biogenesis appears to utilize a yet to be identified pathway, which is different from all currently known small RNA biogenetic pathways. In addition, pilRNAs appear to preferentially target the 3'-UTRs of mRNAs in a partially complementary manner. Our data suggest that pilRNAs, as an integral component of the small RNA transcriptome in somatic cell lineages, represent a distinct population of small RNAs that may have functions similar to germ cell piRNAs.
Project description:PIWI-interacting RNAs (piRNAs), an emergent type of non-coding RNAs during oncogenesis, play critical roles in regulating tumor microenvironment. Systematic analysis of piRNAs' roles in modulating immune pathways is important for tumor immunotherapy. In this study, in-depth analysis of piRNAs was performed to develop an integrated computational algorithm, the immunology piRNA (ImmPI) pipeline, for uncovering the global expression landscape of piRNAs and identifying their regulatory roles in immune pathways. The immunology piRNAs show a tendency towards overexpression patterns in immune cells, causing perturbations in tumors, being significantly associated with infiltration of immune cells, and having prognostic value. The ImmPI score can contribute to prioritizing tumor-related piRNAs and distinguish two subtypes of SKCM (immune-cold and hot phenotypes), as characterized by different prognoses, immunogenicity and antitumor immunity. Finally, we developed an interactive web resource (ImmPI portal: http://www.hbpding.com/ImmPi) for the biomedical research community, with several useful modules to browse, visualize, and download the results of immunology piRNAs analysis. Overall, our work provides a comprehensive landscape of piRNAs across multiple cancer types and sheds light on their regulatory and functional roles in tumor immunity. These findings pave the way for future research and development of piRNA-based immunotherapies for cancer treatment.
Project description:BackgroundPiwi-interacting RNAs (piRNAs) have emerged as potential novel indicators for various diseases; however, their diagnostic value for brucellosis remains unclear. This study aimed to evaluate the diagnostic potential of altered serum piRNAs in patients with brucellosis.MethodsIllumina sequencing via synthesis (SBS) technology was used to screen the serum piRNA profile in brucellosis patients, and markedly dysregulated piRNAs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) assay in two sets from a cohort of 73 brucellosis patients and 65 controls.ResultsIllumina SBS technology results showed that seven piRNAs were markedly elevated in brucellosis patients compared to normal controls. The seven upregulated piRNAs were further validated individually by qRT-PCR, of which three piRNAs (piR-000753, piR-001312, and piR-016742) were confirmed to be significantly and steadily increased in the patients (> 2-fold, P < 0.01). The area under the receiver operating characteristic (ROC) curve (AUCs) for the three piRNAs ranged from 0.698 to 0.783. The AUC for the three piRNAs combination was 0.772, with a specificity of 86% and a positive predictive value of 90%, respectively.ConclusionsThe three-piRNA panel identified in this study has potential as a novel blood-based auxiliary tool for brucellosis detection.