The role of PIWIL4 in breast cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Na Liu
PROVIDER: E-GEOD-78238 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:PIWI proteins bind to PIWI-interacting RNAs (piRNAs) and play key roles in the biogenesis and functions of piRNAs. It has been reported that PIWI proteins are essential for stem cell self-renewal and germline development in diverse organisms, and are ectopically expressed in multiple forms of cancer. However, the role of PIWI in cancer remains elusive. Here we report that one of the four PIWI proteins in humans, PIWIL4, is highly expressed in both breast cancer tissues and the cytoplasm of MDA-MB-231 cell line derived from breast cancer. Reducing PIWIL4 expression drastically impairs migration ability of MDA-MB-231 cells, significantly increases their apotosis, and mildly affects their proliferation. Our transcriptome and proteome analyses reveal that these functions are at least partially achieved via the PIWIL4 regulation of TGF-beta and FGF signaling pathways and major histocompatibility complex (MHC) class II proteins. These findings suggest that PIWIL4 may serve as a potential therapeutic target for breast cancer.
2016-03-08 | GSE78238 | GEO
Project description:PIWI-interacting RNAs (piRNAs) are a novel class of small ncRNAs initially isolated from germ line cells; although recent studies report that they are expressed also in somatic cells. To elucidate the role of piRNAs in somatic cells, in particular from breast cancer, we performed the first extensive next generation sequencing expression analysis of small RNA transcriptomes of hormone responsive breast cancer cell lines in different culture conditions. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GSE39162) database was used. Results led to the identification of ~100 and ~150 human piRNAs in the breast cancerous cell lines and tumors respectively, several of which differentially expressed in cell lines under different experimental conditions tested or in response to ERβ and in tumor tissues. Western blotting and Q-PCR analysis also revealed the presence in breast cell lines of PIWIL (PIWI Like) subfamily members proteins encoded in the human genome (PIWIL2/HILI and PIWIL4/HIWI2) and of other components of the piRNA biogenesis pathways, suggesting that this might indeed be functional in somatic cells. These results show that piRNAs are expressed in human somatic cells, in particular in cancer, where their expression is influenced by neoplastic transformation, growth conditions and estrogen receptor beta. More important, we demonstrate for the first time a distinct pattern of piRNAs expression in cancerous vs normal breast tissues, which suggests a potential role of these epigenetic modulators in mammary carcinogenesis and maintenance of the cancer cell phenotype. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GEO; GSM957192 TAX577740T ,GSM957194 TAX577740N, GSM957195 TAX577453T, GSM957197 TAX577453N, GSM957198 TAX577745T, GSM957200 TAX577745N, GSM957201 TAX577579T, GSM957203 TAX577579N) was used.
2014-10-15 | E-GEOD-56134 | biostudies-arrayexpress
Project description:PIWI-interacting RNAs (piRNAs) are a novel class of small ncRNAs initially isolated from germ line cells; although recent studies report that they are expressed also in somatic cells. To elucidate the role of piRNAs in somatic cells, in particular from breast cancer, we performed the first extensive next generation sequencing expression analysis of small RNA transcriptomes of hormone responsive breast cancer cell lines in different culture conditions. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GSE39162) database was used. Results led to the identification of ~100 and ~150 human piRNAs in the breast cancerous cell lines and tumors respectively, several of which differentially expressed in cell lines under different experimental conditions tested or in response to ERβ and in tumor tissues. Western blotting and Q-PCR analysis also revealed the presence in breast cell lines of PIWIL (PIWI Like) subfamily members proteins encoded in the human genome (PIWIL2/HILI and PIWIL4/HIWI2) and of other components of the piRNA biogenesis pathways, suggesting that this might indeed be functional in somatic cells. These results show that piRNAs are expressed in human somatic cells, in particular in cancer, where their expression is influenced by neoplastic transformation, growth conditions and estrogen receptor beta. More important, we demonstrate for the first time a distinct pattern of piRNAs expression in cancerous vs normal breast tissues, which suggests a potential role of these epigenetic modulators in mammary carcinogenesis and maintenance of the cancer cell phenotype.
2014-10-15 | GSE56134 | GEO
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
Project description:piRNAs function in silencing retrotransposons by associating with the PIWI proteins, AGO3, Aub, and Piwi, in Drosophila germlines. Bioinformatics analyses of piRNAs in Drosophila ovaries suggested that piRNAs are produced by two systems, the primary processing pathway and the amplification loop, from repetitive genes and piRNA clusters in the genome. The amplification loop occurs in a Dicer-independent, PIWI-Slicer-dependent manner. However, the primary processing pathway remains largely conceptual. Here we show that in ovarian somatic cells, which lack Aub and AGO3 but express Piwi, the primary processing pathway for piRNAs indeed exists. Keywords: Small RNA profiling by high throughput sequencing Piwi-associated small RNAs were extracted from Drosophila ovarian somatic cells and their deep sequencing was carried out.
2009-10-01 | E-GEOD-15137 | biostudies-arrayexpress
Project description:Germline-specific Piwi-interacting RNAs (piRNAs) protect the genome against selfish genetic elements and are essential for fertility in animals. piRNAs targeting active transposons are amplified by a feed-forward loop known as the Ping-pong cycle, which links endonucleolytic slicing of target RNAs by Piwi proteins to biogenesis of new piRNAs. However, the biochemical framework for this pathway remains elusive. Here, we describe the identification of a transient Amplifier complex mediating the biogenesis of secondary piRNAs in insect cells. This complex is nucleated by the RNA helicase Vasa and contains the two Piwi proteins participating in the Ping-pong loop, the Tudor protein Qin/Kumo and antisense piRNA guides. These components assemble on the surface of Vasa's helicase domain, which functions as an RNA clamp to anchor Amplifier onto transposon transcripts. We show that ATP-dependent RNP remodelling by Vasa facilitates the transfer of 5'-sliced piRNA precursors between the Ping-pong partners, and failure to achieve this results in Drosophila female sterility. Immunoprecipitated small RNA were purified from untransfected or transfected Bmn4 cells for preparation of high-throughput sequencing libraries.
2014-06-04 | E-GEOD-57420 | biostudies-arrayexpress
Project description:In diverse organisms, the highly-conserved Piwi proteins bind to a complex class of small non-coding RNAs called piRNAs, and are essential for germline stem cell maintenance, transposon silencing, fertility, and offspring viability1. By homology with other Argonautes, Piwi proteins have been proposed and later reported to possess endonuclease activity in vitro, effected by its conserved aspartate catalytic triad2,3. Indeed, mutation of these residues in one of the three mouse PIWI proteins, MILI, affects the production of Line 1 piRNAs and spermatogenesis4. In Drosophila, the conserved slicer function has been proposed to be crucial for all Piwi proteins in piRNA amplification and transposon silencing5. Here, we report in vivo evidence that, in contrast to common belief, the catalytic triad of Piwi is not required for the function of PIwi in the germline for stem cell maintenance, fertility, transposon silencing, or piRNA biogenesis. In addition, it is not required for piRNA biogenesis in the soma where Piwi is the sole Piwi-subfamily protein involved in the process. These observations, together with the recent findings on MILI and MIWI2 triad mutant, indicate that even though the slicer function may be required for a subset of piRNA-mediated process, it is overall inconsequential for the function of Piwi proteins Assess the role of the endonuclease activity of Piwi in all known biological processes that involve Piwi function in Drosophila ovary
2013-02-04 | E-GEOD-34032 | biostudies-arrayexpress
Project description:The onset and progression of breast cancer are linked to genetic and epigenetic changes that alter the normal programming of cells. Epigenetic modifications of DNA and histones contribute to chromatin structure that results in the activation or repression of gene expression. Several epigenetic pathways have been shown to be highly deregulated in cancer cells. Targeting specific histone modifications represents a viable strategy to prevent oncogenic transformation, tumor growth or metastasis. Methylation of histone H3 lysine 4 has been extensively studied and shown to mark genes for expression; however this residue can also be acetylated and the specific function of this alteration is less well known. To define the relative roles of histone H3 methylation (H3K4me3) and acetylation (H3K4ac) in breast cancer, we determined genomic regions enriched for both marks in normal-like (MCF10A), transformed (MCF7) and metastatic (MDA-MB-231) cells using a genome-wide ChIP-Seq approach. Our data revealed a genome-wide gain of H3K4ac associated with both early and late breast cancer cell phenotypes, while gain of H3K4me3 was predominantly associated with late stage cancer cells. Enrichment of H3K4ac was overrepresented at promoters of genes associated with cancer-related phenotypic traits, such as estrogen response and epithelial-to-mesenchymal transition pathways. Our findings highlight an important role for H3K4ac in predicting epigenetic changes associated with early stages of transformation. In addition, our data provide a valuable resource for understanding epigenetic signatures that correlate with known breast cancer-associated oncogenic pathways. RNA-Seq of cell lines MCF10A, MCF7 and MDA-MB-231.
2016-02-10 | E-GEOD-75168 | biostudies-arrayexpress
Project description:Small RNAs exert an effect through diverse RNA interference pathways to transcriptionally or post-transcriptionally silence their targets. The Piwi-interacting RNAs (piRNAs) represent a germline-specific small RNA pathway where Piwi proteins themselves are thought to mediate piRNA biosynthesis. Here, we provide strong evidence for a piRNA amplification loop in zebrafish, in which Ziwi and Zili bind piRNAs of opposite polarity. Furthermore, we describe a function for Zili in transposon defense and germ cell differentiation, as well as a crucial function in meiosis, significantly extending the function of Piwi proteins beyond the control of transposable elements in vertebrates. small RNA from total gonads or Argonaute IPs were cloned and sequenced using 454 GS FLX system.
2008-11-04 | E-GEOD-12547 | biostudies-arrayexpress
Project description:Small RNAs mediate gene silencing by binding Argonaute/Piwi proteins to regulate target RNAs. Here we describe small RNA profiling of the adult testes of Callithrix jacchus, the common marmoset. The most abundant class of small RNAs in the adult testis was piRNAs, while 353 novel miRNAs but few endo-siRNAs were also identified. MARWI, a marmoset homolog of mouse MIWI and a very abundant PIWI in adult testes, associates with piRNAs that show characteristics of mouse pachytene piRNAs. As in other mammals, most marmoset piRNAs are derived from conserved clustered regions in the genome, which are annotated as intergenic regions. However, some of these piRNA cluster regions contain antisense-orientated pseudogenes, suggesting regulation of parental functional protein-coding genes. More piRNAs map to transposable element (TE) subfamilies when they have copies in piRNA clusters. In addition, the strand-bias observed for piRNAs mapped to each TE subfamily correlates with the polarity of copies inserted in clusters. These findings suggest that pachytene piRNA clusters determine the abundance and strand-bias of TE-derived piRNAs, and also regulate protein-coding genes via pseudogene-derived piRNAs. small RNA levels in the adult marmoset testis, and MARWI-IP small RNA levels and RNA levels from the adult marmoset testis with two replicates.
2014-06-01 | E-GEOD-52927 | biostudies-arrayexpress