Specific patterns of PIWI-interacting small noncoding RNA expression changes in dysplastic liver nodules and hepatocellular carcinoma
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ABSTRACT:
PROVIDER: PRJEB11462 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1079340.fastq.gz | Fastqsanger.gz | |||
| ERR1079350.fastq.gz | Fastqsanger.gz | |||
| ERR1079360.fastq.gz | Fastqsanger.gz | |||
| ERR1079370.fastq.gz | Fastqsanger.gz | |||
| ERR1079380.fastq.gz | Fastqsanger.gz |
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Project description:Hepatocellular carcinoma (HCC) is considered the result of a stepwise carcinogenic process, more often beginning with development of premalignant lesions within a cirrhotic liver, morphologically characterized by low- (LGDN) and high-grade (HGDN) dysplastic nodules. Piwi-interacting RNAs (piRNAs) represent a large family of small noncoding (snc) RNAs, 23-35 nucleotide-long, first identified in fruitfly germline cells by their ability to interact with PIWI proteins and thereby exert epigenetic and post-transcriptional regulation of gene expression. The PIWI-piRNAs pathway is active also in human somatic tissues, including stem and cancer cells, where piRNAs and piRNA-like molecules have been shown to influence key cellular processes. We applied small RNA sequencing to search for human liver piRNAs and to profile their expression patterns in cirrhotic nodules (CNs), LGDN, HGDN, early HCC (eHCC) and progressed HCC (pHCC), aiming at identifying possible relationships between these sncRNAs and liver carcinogenesis. Analyzing 54 nodules (14 CN, 8 LGDN, 6 HGDN, 6 eHCC and 20 pHCC) from 17 patients, we identified a 125 piRNA expression signature that clearly discriminates HCC from matched CNs, correlating also to clinicopathological characteristics of HCC. This result was confirmed by functional analysis of predicted piRNA target mRNAs. Interestingly, 24 piRNAs showed specific expression patterns in dysplastic nodules, respect to cirrhotic liver and/or pHCC. These results demonstrate that the piRNA pathway is active in human liver, where it is likely to represent a new player in the molecular events that characterize hepatocellular carcinogenesis, from early stages to pHCC. Furthermore, they suggest that piRNAs might represent new disease biomarkers, potentially useful for differential diagnosis of dysplastic and neoplastic liver lesions.
2016-07-15 | E-MTAB-3973 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is the result of a stepwise process, often beginning with development within a cirrhotic liver of premalignant lesions, morphologically characterized by low- (LGDN) and high-grade (HGDN) dysplastic nodules. PIWI-interacting RNAs (piRNAs) are small noncoding RNAs (sncRNAs), 23-35 nucleotide-long, exerting epigenetic and post-transcriptional regulation of gene expression. Recently the PIWI-piRNA pathway, best characterized in germline cells, has been identified also in somatic tissues, including stem and cancer cells, where it influences key cellular processes.Small RNA sequencing was applied to search for liver piRNAs and to profile their expression patterns in cirrhotic nodules (CNs), LGDN, HGDN, early HCC and progressed HCC (pHCC), analyzing 55 samples (14 CN, 9 LGDN, 6 HGDN, 6 eHCC and 20 pHCC) from 17 patients, aiming at identifying possible relationships between these sncRNAs and liver carcinogenesis. We identified a 125 piRNA expression signature that characterize HCC from matched CNs, correlating also to microvascular invasion in HCC. Functional analysis of the predicted RNA targets of deregulated piRNAs indicates that these can target key signaling pathways involved in hepatocarcinogenesis and HCC progression, thereby affecting their activity. Interestingly, 24 piRNAs showed specific expression patterns in dysplastic nodules, respect to cirrhotic liver and/or pHCC.The results demonstrate that the PIWI-piRNA pathway is active in human liver, where it represents a new player in the molecular events that characterize hepatocarcinogenesis, from early stages to pHCC. Furthermore, they suggest that piRNAs might be new disease biomarkers, useful for differential diagnosis of dysplastic and neoplastic liver lesions.
| S-EPMC5342370 | biostudies-literature
Project description:Small noncoding (snc) RNAs represent a growing family of transcripts that regulate key cellular processes, including mRNA degradation, translational repression and transcriptional gene silencing. Among these, the PIWI-interacting RNAs (piRNAs), a major class of sncRNAs initially identified in the germline of a variety of species, are now being found to be functionally active also in somatic cells. However, whether the Piwi/piRNA pathway is associated with fundamental biological processes, such as cell cycle progression, remains elusive. Here we investigated the possibility that piRNAs are expressed in liver and modulated during regenerative proliferation of this organ. To this aim, smallRNA-Seq was applied to identify and quantitate expression of these RNAs in rat liver before, during and after the wave of cell proliferation that follows partial hepatectomy (PH). Q-PCR analysis revealed the presence in rat liver of two PIWI (PIWI-Like) subfamily members (PIWIL2/HILI and, to a much lower level, PIWIL4/HIWI2) and other components of the piRNA biogenesis pathways, suggesting that this is present and functional in hepatocytes. Indeed, ~1400 piRNAs originally identified in rat and other mammalian germline cells are expressed in adult rat liver, including 72 that show timed changes in expression during cell cycle progression. Most piRNAs are up-regulated 24-48h after hepatectomy, a timing that corresponds to cell transition through the S phase, and return to basal levels by 168 h, when organ regeneration is completed and hepatocytes reach quiescence. These results indicate that the piRNA pathway is active in somatic cells and, more important, that it is subject to regulation during physiological processes, such as cell proliferation, when piRNAs may exert their regulatory functions on the cell genome and transcriptome. smallRNA-Seq was applied to identify and quantitate expression of RNAs in rat liver before and after partial hepatectomy (PH).
2014-06-17 | E-GEOD-55783 | biostudies-arrayexpress
Project description:Small noncoding (snc) RNAs represent a growing family of transcripts that regulate key cellular processes, including mRNA degradation, translational repression and transcriptional gene silencing. Among these, the PIWI-interacting RNAs (piRNAs), a major class of sncRNAs initially identified in the germline of a variety of species, are now being found to be functionally active also in somatic cells. However, whether the Piwi/piRNA pathway is associated with fundamental biological processes, such as cell cycle progression, remains elusive. Here we investigated the possibility that piRNAs are expressed in liver and modulated during regenerative proliferation of this organ. To this aim, smallRNA-Seq was applied to identify and quantitate expression of these RNAs in rat liver before, during and after the wave of cell proliferation that follows partial hepatectomy (PH). Q-PCR analysis revealed the presence in rat liver of two PIWI (PIWI-Like) subfamily members (PIWIL2/HILI and, to a much lower level, PIWIL4/HIWI2) and other components of the piRNA biogenesis pathways, suggesting that this is present and functional in hepatocytes. Indeed, ~1400 piRNAs originally identified in rat and other mammalian germline cells are expressed in adult rat liver, including 72 that show timed changes in expression during cell cycle progression. Most piRNAs are up-regulated 24-48h after hepatectomy, a timing that corresponds to cell transition through the S phase, and return to basal levels by 168 h, when organ regeneration is completed and hepatocytes reach quiescence. These results indicate that the piRNA pathway is active in somatic cells and, more important, that it is subject to regulation during physiological processes, such as cell proliferation, when piRNAs may exert their regulatory functions on the cell genome and transcriptome.
2014-06-17 | GSE55783 | GEO
Project description:Background: PIWI-interacting RNAs (piRNAs), the largest class of noncoding RNAs in mammals, cooperate with PIWI proteins to safeguard the genome from insertional mutations during germline development. Although a growing number studies have linked the PIWI-piRNA pathway to carcinogenesis, the role of piRNAs in glioma has not been explored. Methods: Utilizing directly measured and imputed genotypes from the GliomaScan genome-wide association study (1,840 cases and 2,401 controls), genetic variants in 1,428 piRNAs were analyzed for association with glioma risk. In vitro assays were performed to interrogate the functional impact of a top identified piRNA and its variant allele. Results: Variants in five piRNAs were considered to be associations of interest and four of these showed narrow clusters of enhanced association signals surrounding the index variant. Functional analyses of one of these piRNAs, piR-598, revealed that transfection of the wild-type piRNA impacted expression of genes involved in cell death/survival, and reduced glioma cell viability and colony formation. However, upon delivery of piR-598 containing the variant allele at rs147061479 (OR=1.80; 95% CI: 1.33-2.46; P=1.69 x 10-4), cell proliferation was sharply increased. Conclusions: These findings suggest that variant rs147061479 in piR-598 increases glioma risk by abolishing the tumor-suppressive function of piR-598, instead conferring growth-promoting properties that may result from a shift in piRNA targets. Impact: This transdisciplinary study demonstrates a role of piRNAs in gliomagenesis by evidence from both post-GWAS and in vitro functional analyses, and supports expanded investigation into the link between the PIWI-piRNA pathway and cancer.
2016-06-04 | GSE78935 | GEO
Project description:Decoding the 5’ nucleotide bias of PIWI-interacting RNAs (piRNAs)
| PRJNA476241 | ENA
Project description:Various small RNA libraries from purified microtubules or Xiwi immunoprecipitates or total extract from X.tropicalis or X.laevis egg extract. Various small RNA libraries from single X.tropicalis eggs. Analysis of this series of files is described in the manuscript "Systematic and single cell analysis of Xenopus Piwi-interacting RNAs and Xiwi".
2009-09-01 | GSE15556 | GEO
Project description:PIWI-interacting RNAs as novel regulators of pancreatic beta-cell function
| PRJNA362355 | ENA
Project description:Various small RNA libraries from purified microtubules or Xiwi immunoprecipitates or total extract from X.tropicalis or X.laevis egg extract. Various small RNA libraries from single X.tropicalis eggs. Analysis of this series of files is described in the manuscript "Systematic and single cell analysis of Xenopus Piwi-interacting RNAs and Xiwi". Small RNAs were ligated with linkers and converted to cDNA by reverse transcription. cDNA library was amplified by PCR and was sequenced with either the 454 Genome Sequencer FLX platform or the Illumina GA-II platform.
2009-08-31 | E-GEOD-15556 | biostudies-arrayexpress
Project description:There have been substantial researches focused on the roles of microRNAs (miRNA) and Piwi-interacting RNAs (piRNA) delivered from mammalian spermatozoa, comparatively little is known about the role of sperm-delivered miRNAs and piRNAs within cockerels’ (breeding cock) sperm. A small RNA library of cockerels’ sperm was constructed using Illumine high-throughput sequencing technology.
2018-12-14 | GSE108121 | GEO