Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PiRNA-independent Function of PIWIL1 as a Novel co-activator for Anaphase Promoting Complex/Cyclosome (APC/C) to Drive Pancreatic Cancer Metastasis

ABSTRACT: Piwi proteins are normally restricted in germ cells to suppress transposons through association with piRNAs, but are also frequently activated in many types of human cancers. Of great puzzle is the lack of induction of corresponding piRNAs in cancer cells, as we document here in human pancreatic ductal adenocarcinomas (PDAC), implying that such germline-specific proteins are somehow hijacked to promote tumorigenesis through different mode of action. To pursue the underlying mechanism, we now demonstrate that in the absence of piRNAs, the aberrantly induced human PIWIL1 in PDAC functions as an oncoprotein by activating the Anaphase Promoting Complex/Cyclosome (APC/C), which then targets a critical cell adhesion-related protein Pinin to enhance PDAC metastasis. This is in contrast to piRNA-dependent PIWIL1 ubiquitination and removal by APC/C during late spermiogenesis. These findings thus unveil an piRNA-dependent mechanism to switch PIWIL1 from a substrate in spermatids to a co-activator of APC/C in human cancer cells.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE141340 | GEO | 2020/02/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Piwi proteins and piRNAs in mammalian oocytes and early embryos

Project description:Germ cells of most animals critically depend on piRNAs and Piwi proteins. Surprisingly, piRNAs in mouse oocytes are relatively rare and dispensable. We present compelling evidence for strong Piwi-piRNA expression in oocytes of other mammals. Human fetal oocytes express PIWIL2 and transposon-enriched piRNAs. Oocytes in adult human ovary express PIWIL1 and PIWIL2, while those in bovine ovary just express PIWIL1. In human, macaque and bovine ovaries we find piRNAs that resemble testis-borne pachytene piRNAs. Isolated bovine follicular oocytes were shown to contain abundant, relatively short piRNAs that preferentially target transposable elements. Using label-free quantitative proteome analysis we show that these maturing oocytes strongly and specifically express the thus-far uncharacterized PIWIL3 protein, alongside other known piRNA-pathway components. In bovine early embryos these piRNAs are still abundant, revealing a potential impact of piRNAs on mammalian embryogenesis. Our results reveal unexpected, highly dynamic piRNA pathways in mammalian oocytes and early embryos. Analyses of multiple small RNA libraries obtained from fetal/adult oocytes, cumulus cells, ovary, testis and 2-4 cell stage ivf embryos of multiple mammalian species.

2015-03-27 | E-GEOD-64942 | biostudies-arrayexpress

Piwi proteins and piRNAs in mammalian oocytes and early embryos

2015-03-27 | GSE64942 | GEO

RNA-Immunoprecipitation of PIWIL1/piRNA complexes in COLO 205 cells and deep-sequencing of associated small RNAs with NGS technologies

Project description:To evaluate PIWIL1/piRNAs association in the metastatic COLO 205 cell line, we performed an RNA-immunoprecipitation experiment followed by small RNA deep-sequencing (RIP-Seq). For the identification of PIWIL1/piRNA complexes, independent reactions were carried out with two different antibodies (IP1 and IP2); non-specific interactions were computationally filtered out using a No Antibody control (No Ab).

2020-08-05 | E-MTAB-8121 | biostudies-arrayexpress

piRNA-independent Function of PIWIL1 as a Novel co-activator for Anaphase Promoting Complex/Cyclosome (APC/C) to Drive Pancreatic Cancer Metastasis

Project description:piRNA-independent Function of PIWIL1 as a Novel co-activator for Anaphase Promoting Complex/Cyclosome (APC/C) to Drive Pancreatic Cancer Metastasis

| PRJNA593186 | ENA

The non-redundant functions of PIWI family proteins in gametogenesis in golden hamsters

Project description:The piRNA pathway is essential for female fertility in golden hamsters and likely humans, but not in mice. However, the role of individual PIWIs in reproduction remains poorly understood outside of mice. Here, using golden hamsters, we establish dynamic expression profiles and subcellular localization for all four PIWIs and characterize their associated reproductive defects in knockout mutants. In female golden hamsters, PIWIL1 and PIWIL3 are highly expressed throughout oogenesis and early embryogenesis, while PIWIL1 knockout leads to sterility, and PIWIL3 deficiency results in subfertility with lagging zygotic development. PIWIL1 can partially compensate for TE silencing and transcriptional regulation in PIWIL3 knockout females, but not vice versa. PIWIL1 and PIWIL4 are the predominant PIWIs expressed in adult or postnatal testes, respectively, while PIWIL2 is present in both stages. Notably, in golden hamsters, none of the differences were found between pre-pachytene and pachytene piRNAs characteristic of mice. Loss of any PIWI expressed in testes leads to sterility and severe but distinct spermatogenesis disorders, which are markedly less severe in mice. These findings expand our understanding of the non-redundant PIWI-piRNA regulatory functions in gametogenesis and early embryogenesis in golden hamster, increasing the value of this model for studying human fertility.

2023-07-13 | GSE217621 | GEO

piRNA pathway is essential for generating functional oocytes in golden hamster

Project description:Piwi-interacting RNAs (piRNAs) are small RNAs predominantly expressed in germ cells that function in gametogenesis in various species. Notably, PIWI-deficient female mice are fertile and mouse oocytes express a panel of small RNAs that do not appear widely representative of mammals. Thus, the function of piRNAs in mammalian oogenesis remains largely elusive. Here, we generated PIWIL1- and MOV10L1-deficient golden hamsters and found that all female and male mutants were sterile, with severe defects in embryogenesis and spermatogenesis, respectively. PIWIL1-deficient oocytes displayed aberrant transposon accumulation and broad transcriptomic dysregulation, and maternal PIWIL1-deficient embryos had impaired zygotic genome activation (ZGA). Moreover, our results support that PIWIL1-piRNAs exert a non-redundant function in silencing endogenous retroviruses (ERVs) in oocytes. Together, our findings demonstrate that piRNAs are indispensable for generating functional germ cells in golden hamsters and show the informative value of this model species for functional and mechanistic investigations of piRNAs in gametogenesis, especially those related to female infertility.

2021-08-02 | GSE169528 | GEO

The Anaphase Promoting Complex/Cyclosome degrades DMS3 to maintain RNA-directed DNA Methylation in Arabidopsis [lncRNA-seq]

Project description:RNA-directed DNA methylation (RdDM) plays an essential role in transposable element (TE) silencing in plants. In the Arabidopsis RdDM pathway, the DDR complex containing DRD1, DMS3, and RDM1, is necessary for recruiting Pol V to transcribe scaffold RNA. Although the role of DDR is known, the mechanism by which the DDR complex is regulated remains unexplored. Here, we demonstrate that the Anaphase Promoting Complex/Cyclosome (APC/C) monitors the assembly of the DDR complex by targeting DMS3 for degradation. We show that a subset of Pol V-dependent RdDM loci are de-repressed in apc/c mutants, accompanied by defective recruitment and transcription of Pol V. APC/C targets DMS3 for ubiquitination and degradation in a D box-dependent manner, and the D-box-mutated DMS3 fails to complement the dms3 mutant. Competitive binding assays shows that the dosage of DMS3 is critical for the assembly of the DDR complex, and in vivo gel filtration analysis shows that the assembly of both DDR and Pol V is compromised in the apc8 mutant. These findings uncover a safeguard role of APC/C-mediated DMS3 degradation in the assembly of the DDR complex, and provide a direct link between selective protein degradation and RdDM.

2019-01-31 | GSE106970 | GEO

The Anaphase Promoting Complex/Cyclosome degrades DMS3 to maintain RNA-directed DNA Methylation in Arabidopsis [small RNA-seq]

2019-01-31 | GSE106971 | GEO

A piRNA like small RNA interacts with and modulates p-ERM proteins in human somatic cells

Project description:PIWI-interacting RNAs (piRNAs) are thought to silence transposon and gene expression during development. However, the roles of piRNAs in somatic tissues are largely unknown. Here we report the identification of 555 piRNAs in human lung bronchial epithelial (HBE) and non-small cell lung cancer (NSCLC) cell lines, including 295 that don’t exist in databases termed as piRNA-Like sncRNAs or piRNA-Ls. Distinctive piRNA/piRNA-L expression patterns are observed between HBE and NSCLC cells. piRNA-L-163 (piR-L-163), the top down-regulated piRNA-L in NSCLC cells, binds directly to phosphorylated ERM proteins (p-ERM), which is dependent on the central part of UUNNUUUNNUU motif in piR-L-163 and the RRRKPDT element in ERM, and. The piR-L-163/p-ERM interaction is critical for p-ERM’s binding capability to filamentous actin (F-actin) and ERM-binding phosphoprotein 50 (EBP50). Thus, piRNA/piRNA-L may play a regulatory role through direct interaction with proteins in physiological and pathophysiological conditions.

2015-09-03 | PXD002076 | Pride

Deep sequencing and high-throughput analysis of PIWI-associated small RNAs

Project description:Small RNAs are now known to be major regulatory factors of gene expression. Emerging methods based on deep-sequencing have enabled the analysis of small RNA expression in a high-throughput manner, leading to the identification of large numbers of small RNAs in various species. Moreover, profiling small RNA data together with transcriptome data enables transcriptional and post-transcriptional regulation mediated by small RNAs to be hypothesized. Here, we isolated PIWIL1 (MIWI)-associated small RNAs from mouse testes, and performed small RNA-seq analysis. In addition, directional RNA-seq was performed using Piwil1 mutant mouse testes. Using these data, we describe protocols for analyzing small RNA-seq reads to obtain profiles of small RNAs associated with PIWI proteins. We also present bioinformatic protocols for analyzing RNA-seq reads that aim to annotate expression of piRNA clusters and identify genes regulated by piRNAs.

2017-05-25 | GSE97195 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data